Showing papers on "Epinephrine published in 1977"
TL;DR: It is concluded that dopamine is secreted into hypophysial portal blood in significant quantities during pregnancy, that hypothalamic secretion of dopamine in cyclic rats is greatest during the day of estrus and early diestrus and at least on theDay of proestrus, and that these findings support the view that dopamine of hypothalamic origin may have an important role in the regulation of anterior pituitary function.
Abstract: Catecholamine levels in hypophysial portal plasma were determined in pregnant and non-pregnant female rats as well as in intact and castrated male rats, using a radioenzymatic assay for the simultaneous determination of dopamine, norepinephrine, and epinephrine in 50 mul of plasma. Portal and arterial blood were collected from anesthetized rats at 7 mul/min for 60 min. During the collection, blood was kept at 0 C, a temperature at which endogenous catecholamines were relatively stable. Dopamine was present in high concentrations in hypophysial portal plasma thorughout pregnancy, attaining a level near 20 ng/ml on the 20th day of gestation. Dopamine levels in arterial plasma from the same rats were low or undetectable (0.4--0.8 ng/ml1. Norepinephrine and epinephrine was undetectable (less than 0.6 ng/ml) in portal as well as arterial plasma from these rats. The major catecholamine in extracts of the hypothalamus from pregnant rats was norepinephrine, whereas that in the posterior pituitary was dopamine. Dopamine levels in portal plasma collected during proestrus, estrus, diestrus 1, and diestrus 2, were 1.32 +/- 0.21 (mean +/- SE), 3.87 +/- 0.96, 3.11 +/- 0.73, and 2.3 +/- 0.45, respectively. Dopamine in portal plasma from intact and from castrated male rats was approximately 0.6 ng/ml. Norepinephrine and epinephrine were not detectable in either portal or arterial plasma from these animals. It is concluded 1) that dopamine is secreted into hypophysial portal blood in significant quantities during pregnancy, 2) that hypothalamic secretion of dopamine in cyclic rats is greatest during the day of estrus and early diestrus and at least on the day of proestrus, and 3) that these findings support the view that dopamine of hypothalamic origin may have an important role in the regulation of anterior pituitary function.
369 citations
TL;DR: The finding of significantly raised plasma adrenaline concentrations in a large proportion of hypertensive patients supports the hypothesis that the activity of the sympathetic nervous system is increased in essential hypertension.
Abstract: Plasma adrenaline, noradrenaline, and dopamine concentrations and plasma renin activity were measured in the supine position and after standing for 10 minutes in 14 patients with sustained benign essential hypertension and in five patients with labile hypertension. Results were compared with values obtained in 11 normotensive control subjects. In controls plasma noradrenaline concentrations increased with age, while plasma adrenaline values tended to decrease with age. No significant difference in mean plasma noradrenaline was found between hypertensive and control subjects, but plasma noradrenaline seemed slightly increased in a proportion of hypertensive patients aged less than 50. Plasma adrenaline was considerably raised in both supine and standing positions in eight patients with sustained hypertension and in two with labile hypertension. Dopamine concentrations and plasma renin activity were similar in all groups studied. The finding of significantly raised plasma adrenaline concentrations in a large proportion of hypertensive patients supports the hypothesis that the activity of the sympathetic nervous system is increased in essential hypertension. Measurement of plasma adrenaline seems to be a more sensitive index of this activity than that of plasma noradrenaline.
204 citations
TL;DR: Progesterone-induced decrease in the number of uterinealpha adrenergic receptors provides a potential explanation for the reduced alpha adrenergic contractile response to epinephrine in the progester one-primed myometrium.
Abstract: The effects of estrogen and progesterone on uterine alpha-adrenergic receptors were investigated by direct receptor-binding studies. Immature female rabbits were primed with estrogen by intramuscular injections for 4 days. Other rabbits were primed with progesterone by injections of estrogen for 4 days followed by injections of progesterone for 4 days. The alpha adrenergic antagonist, [3H]dihydroergocryptine, was used to directly assess the number and affinity of alpha adrenergic receptors in membranes derived from estrogen-and progesterone-primed uteri. Membranes from estrogen-primed uteri contained 257 +/- 52 fmol of [3H]dihydroergocryptine-binding sites per mg protein whereas membranes from progesterone-primed uteri contained 83 +/- 11 fmol of of binding sites per mg protein. This reduction of alpha adrenergic receptor-binding sites by progesterone was statistically significant (P less than 0.02). In contrast, no significant difference in the binding site affinity was observed between the estrogen- and progesterone-primed groups. The progesterone-induced decrease in the number of uterine alpha adrenergic receptors provides a potential explanation for the reduced alpha adrenergic contractile response to epinephrine in the progesterone-primed myometrium.
145 citations
TL;DR: There are a- and β-adrenergic effects on Purkinje fiber automaticity; the former decrease and the latter increase rate; the effects on automaticity of /3- adrenergic amines are greater in the neonates than in the adult.
Abstract: We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. Control spontaneous rates for adults and neonates did not differ significantly. There was a biphasic response to all agonists such that rate decreased at low and increased at high concentrations. The decrease was greater with phenylephrine and epinephrine than with isoproterenol. The increase in rate was greater with isoproterenol and epinephrine than with phenylephrine. Propranolol shifted the dose-response curves downward and to the right for all agonists; phentolamine, shifter the curves upward and to the left. Epinephrine and isoproterenol dose-response curves for the neonates were upward and to the left of those for adults. Phenylephrine curves were identical for adults and neonates. Thus there are alpha- and beta-adrenergic effects on Purkinje fiber automaticity; the former decrease and the latter increase rate. Furthermore, the effects on automiticity of beta-adrenergic amines are greater in the neonates than in the adult.
137 citations
TL;DR: While the sympathetic response during marked hypoglycemia may have been initiated by alterations in cerebal metabolism, the feeding response evidently was not, and a decrease in the utilization of glucose per se does not appear to be the critical stimulus in either case.
Abstract: Intravenous infusions of manose or B-hydroxybutyrate, metabolic fuels which can be oxidized by brain, abolished adrenal discharge of epinephrine in rats during insulin-induced hypoglycemia, whereas infusion of fructose, a sugar which does not cross the blood-brain barrier, did not. In contrast, increased feeding behavior during hypoglycemia was prevented both by the sugars and by B-hydroxybutyrate. Thus, while the sympathetic response during marked hypoglycemia may have been initiated by alterations in cerebal metabolism, the feeding response evidently was not, and a decrease in the utilization of glucose per se does not appear to be the critical stimulus in either case.
135 citations
TL;DR: The inhibitory effect of epinephrine on (45)Ca(++) uptake and insulin release appeared to be mediated via an alpha-adrenergic mechanism, since is was abolished in the presence of phentolamine.
Abstract: The effects of somatostatin and epinephrine have been studied with regard to glucose-induced insulin release and 45Ca++ uptake by rat pancreatic islets after 2 days in tissue culture and with regard to 45Ca++ efflux from islets loaded with the radio-isotope during the 2 days of culture. 45Ca++ uptake, measured simultaneously with insulin release, was linear with time for 5 min. 45Ca++ efflux and insulin release were also measured simultaneously from perifused islets.
Glucose (16.7 mM) markedly stimulated insulin release and 45Ca++ uptake. Somatostatin inhibited the stimulation of insulin release by glucose in a concentration-related manner (1-1,000 ng/ml) but was without effect on the glucose-induced stimulation of 45Ca++ uptake. Similarly, under perifusion conditions, both phases of insulin release were inhibited by somatostatin while no effect was observed on the pattern of 45Ca++ efflux after glucose.
Epinephrine, in contrast to somatostatin, caused a concentration-dependent inhibition of the stimulation of both insulin release and 45Ca++ uptake by glucose. Both phases of insulin release were inhibited by epinephrine and marked inhibition could be observed with no change in the characteristic glucose-evoked pattern of 45Ca++ efflux (e.g., with 10 nM epinephrine). The inhibitory effect of epinephrine on 45Ca++ uptake and insulin release appeared to be mediated via an α-adrenergic mechanism, since is was abolished in the presence of phentolamine.
Somatostatin inhibits insulin release without any detectable effect upon the handling of calcium by the islets. In contrast, inhibition of insulin release by epinephrine is accompanied by a partial inhibition of glucose-induced Ca++ uptake.
109 citations
TL;DR: Maternal analgesia and anesthesia influenced plasma catecholamine levels, and significant elevations of plasma epinephrine and norepinephrine were found in three phases of labor.
105 citations
TL;DR: In this paper, the authors showed that the diminution of the exercise-induced decline in glucose concentrations correlated significantly with the diminutions of the glucagon as well as the epinephrine responses.
Abstract: Seven men ran at 60% of individual maximal oxygen uptake to exhaustion during beta-adrenergic blockade with propranolol or without drugs. After propranolol administration the increases during exercise in plasma glucagon and epinephrine concentrations as well as the decrease in plasma glucose concentrations were faster than in control experiments. When euglycemia was maintained by glucose infusion during beta-adrenergic blockade, glucagon and epinephrine responses to exercise, although not abolished, were markedly reduced. The diminution of the exercise-induced decline in glucose concentrations correlated significantly with the diminution of the glucagon as well as the epinephrine responses. Thus decreased glucose concentrations may significantly enhance the secretion of glucagon and epinephrine during prolonged exercise in man. Since the diminution of the glucagon response produced by glucose infusion was not accompanied by significant alterations in the levels of nonesterified fatty acid (NEFA) and glycerol, increased glucagon secretion does not seem to be a major determinant of lipolysis during exercise in man. During glucose infusion, glycogen utilization rates in muscle (n = 4) tended to decrease, whereas carbohydrate combustion rate and concentrations of norepinephrine, insulin, alanine, and lactate were unchanged.
104 citations
TL;DR: The data demonstrate enhanced rather than impaired sensitivity to catecholamines in diabetes mellitus, and suggest that an alpha-cell glucoreceptor defect may account for the abnormal response to glucopenia in diabetics.
Abstract: To examine the role of catecholamines in glucopenia-induced glucagon secretion, urinary epinephrine and norepinephrine and plasma immunoreactive glucagon (IRG) were measuredduring insulin-induced hypoglycemia in normal and insulin-dependent diabetic man. Despite equivalent levels of hypoglycemia the mean plasma IRG increment in diabetics was only 15% of normals. The increases in epinephrine and norepinephrine were comparable in diabetics and normals; thus, the blunted response in plasma IRG to the stimulus of low blood sugar in diabetics cannot be explained by a generalized defect in catecholamine secretion. It is suggested that an alpha-cell glucoreceptor defect may account for the abnormal response to glucopenia in diabetics. To evaluate the possibility that impaired sensitivity to circulating catecholamines could explain the alpha cell dysfunction in diabetics, exogenous epinephrine was infused in normals and insulindependent diabetics. Elevated plasma IRG during epinephrine infusion was observed in on...
100 citations
TL;DR: These cells now provide an excellent system for studying cell surface regulation of hormone and neurotransmitter release and are show the isolated bovine chromaffin cells to be viable, functioning, and available in large quantity.
Abstract: Bovine adrenal chromaffin cells were isolated by removal of the cortex and sequential collagenase digestion of the medulla. The catecholamine secretory function of these cells was characterized with respect to acetylcholine stimulation, cation requirements, and cytoskeletal elements. The dose-response curve for stimulated release had its half-maximum value at 10-5 M acetylcholine, and maximum secretion was on the average 7 times that of control basal secretion. The differential release of epinephrine versus norepinephrine after stimulation with 0.1 mM acetylcholine occurred in proportion to their distribution in the cell suspension. The cholinergic receptors were found to be predominantly nicotinic. The kinetics of catecholamine release were rapid, with significant secretion occurring in less than 60 sec and 85% of maximum secretion within 5 min. A critical requirement for calcium in the extracellular medium was demonstrated, and 80% of maximum secretion was achieved at physiologic calcium concentrations. Stimulation by excess potassium (65 mM KCl) also induced catecholamine secretion which differed from acetylcholine stimulation in being less potent, in having a different dependence on calcium concentration, and in its response to the local anesthetic tetracaine. Tetracaine, which is thought to inhibit membrane cation permeability, was able to block acetylcholine-stimulated but not KCl-stimulated secretion. The microtubule disrupting agent vinblastine was able to block catecholamine release whereas the microfilament disrupter cytochalasin B had little effect. The results show the isolated bovine chromaffin cells to be viable, functioning, and available in large quantity. These cells now provide an excellent system for studying cell surface regulation of hormone and neurotransmitter release.
97 citations
TL;DR: The sympatho-adrenal system contributes to the regulation of metabolism in a wide variety of physiological and pathophysiological states, and catecholamines mediate some of the metabolic responses in hypoglycaemia, exercise, cold exposure, and haemorrhagic shock.
TL;DR: A technique of perfusing the isolated head of trout with a constant-fluid flow was used to study adrenergic factors controlling the vasomotricity of the gill, and it was shown that only alpha-vasoconstrictor adrenoreceptors occur in this region.
Abstract: A technique of perfusing the isolated head of trout with a constant-fluid flow was used to study adrenergic factors controlling the vasomotricity of the gill. The use of adrenergic blockers (phentolamine 10(-4) M and propranolol 10(-4) M) enabled the vascular effect of epinephrine to be split into two components: an alpha-vasoconstrictor effect superimposed upon the dominant beta-vasodilator effect. Effect alpha appears more rapidly than effect beta and causes an initial vasoconstriction. Under constant-flow perfusion the effect of epinephrine on the efferent arterial and venous flows is a diminution of the venous flow and an increase of the arterial. This is the result of closure of the anastomoses between the efferent artery and the central compartment of the filament. It was shown that only alpha-vasoconstrictor adrenoreceptors occur in this region.
TL;DR: The results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types.
Abstract: We determined the effect of alpha-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of alpha-adrenergic receptors with either phenylephrine (10(-8) M to 10(-6) M) or epinephrine (10(-8) M to 10(-6) M) plus propranolol (10(-6) M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10(-6) M). Phenylephrine (10(-5)M attenuated cyclic AMP generation in response to isoproterenol (10(-8) M and 10(-5) M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10(-6) M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by beta-adrenergic receptors, whereas decreases appear to by mediated by alpha-adrenergic receptors.
TL;DR: Splanchnic nerve stimulation appears to be the most important determinant of adrenomedullary function, and is the physiological stimulus for catecholamine secretion.
TL;DR: It is concluded that a single injection of B. pertussis into rats results in a sustained modification of insulin secretory processes in the pancreatic beta-cells in such a manner as to favor insulinsecretory responses to beta-adrenergic stimulation and other secretagogues.
Abstract: In order to study the mechanism by which pertussis-sensitized rats showed enhanced insulin secretory responses to various secretagogues (Sumi, T., and M. Ui, Endocrinology 97: 352, 1975), pancreases of rats receiving a single injection of Bordetella pertussis cells 3 days before were perfused with Krebs-Ringer solution, and release of insulin therefrom was compared with that from the pancreases of normal rats. Much more insulin was released from the pancreas of the pertussis-sensitized rat than from the pancreas of the normal rat in response to glucose, arginine, glibenclamide and 3-isobuty-l-methylxanthine. The inhibition of insulin secretion caused by epinephrine, norepinephrine or phenylephrine via alpha-adrenergic receptors in the pancreas of normal rats was no longer observable with the pancreas from pertussis-sensitized rats. Instead, the addition of epinephrine with or without phentolamine gave rise to a marked secretion of insulin from the pancreas of pertussis-sensitized rats which was prevented by propranolol. It is concluded that a single injection of B. pertussis into rats results in a sustained modification of insulin secretory processes in the pancreatic beta-cells in such a manner as to favor insulin secretory responses to beta-adrenergic stimulation and other secretagogues.
TL;DR: Adenosine is shown to have a modulating effect upon basal and hormone-stimulated lipolysis in the perifusion system and sufficient endogenous adenosine (<0.01 muM) is present to maximally affect basallipolysis.
Abstract: Incubation of isolated rat epididymal fat cells is associated with the accumulation of adenosine in the incubation medium. To more clearly define the effect of adenosine on lipolysis, isolated rat epididymal adipocytes were studied with the perifusion system.
Various combinations of epinephrine, adenosine, and adenosine deaminase were perifused through the adipocytes. Exogenous adenosine, 0.001-10.0 μM, had no discernible influence upon unstimulated lipolysis; but exogenous adenosine inhibited epinephrine-sensitive lipolysis in a concentration-dependent manner. Cells perifused with 0.3 μM epinephrine plus 0.001 μM adenosine did not show any impairment of the lipolytic response to 0.3 μM epinephrine alone. Adenosine, 0.01 μM, inhibited the response to epinephrine by 50%; response to 0.3 μM epinephrine plus 0.1 μM adenosine was similar to the basal rate.
Perifusion with adenosine deaminase significantly increased basal lipolysis to 30% of the epinephrine response. Adenosine deaminase and epinephrine were synergistic in stimulating lipolysis to 180% of the response to epinephrine alone. Isolated fat cells were incubated for 30 min, and the cell-free used medium was perifused through fresh fat cells. Epinephrine in used medium was less effective in promoting lipolysis than epinephrine in fresh buffer. High-pressure liquid chromatography identified adenosine in the used medium. Bovine serum albumin possessed adenosine deaminase activity but accounted for negligible conversion of adenosine to inosine.
Adenosine is shown to have a modulating effect upon basal and hormone-stimulated lipolysis in the perifusion system. Sufficient endogenous adenosine (<0.01 μM) is present to maximally affect basal lipolysis. Hormone-stimulated lipolysis, although inhibited somewhat by endogenous adenosine, requires the addition of exogenous adenosine for complete inhibition.
TL;DR: It is concluded that epinephrine alters branchial vascular flow and functional surface area via alpha- and beta-adrenergic receptors, but also increases branchial permeability to water and probably urea, via beta-adsenergic receptors.
Abstract: In isolated trout heads, perfused at constant pressure, epinephrine (10(-6) M) was found to double water and urea efflux but increased Ringer perfusion rate by only 33%. Drastic changes in perfusion rate (by clamping) produced smaller changes of both efflux rates. Epinephrine-stimulated increase in water and urea efflux, and perfusion rate, was blocked by propranolol (beta-blocker) but not by phentolamine (alpha-blocker). Both blockers together canceled out all epinephrine effects. Epinephrine increased water influx across isolated unperfused gill arches, the effect again being blocked by propranolol but not by phentolamine. Both blockers together canceled any epinephrine effect. We conclude that epinephrine alters branchial vascular flow and functional surface area via alpha- and beta-adrenergic receptors, but also increases branchial permeability to water and probably urea, via beta-adrenergic receptors. To test the validity of the perfused head technique, water and urea efflux rates were compared with in vivo values.
TL;DR: The epinephrine levels in the brain appear to be under similar biosynthetic control as in the adrenal glands.
TL;DR: The effects of adrenergic and cholinergic stimulation upon 45Ca2+ fluxes in isolated parotid acinar cells were described and direct measurement of Ca2+ efflux indicated that the increased calcium uptake in the presence of epinephrine was not the indirect result of a decrease in efflux.
TL;DR: The authors conclude that the sympathetic nervous system is involved in porcine MH only as a secondary response to stress; that conduction anesthesia will not protect pigs from MH; and that the efficacy of dantrolene in porCine MH is due to its effects on skeletal muscle rather than to depression of the sympathy nervous system.
Abstract: Malignant hyperthermia (MH) is characterized in part by sympathetic hyperactivity associated with increased levels of circulating catecholamines. Controversy exists as to whether the sympathetic nervous system is in some way abnormal and primarily contributing to MH, or whether the sympathetic response is secondary to the stress of MH originating from skeletal muscle. Total spinal anesthesia with resulting sympathetic denervation was used in genetically susceptible Poland China swine to investigate this question. isobaric tetracaine, 1.2–2.2 mg/kg, was injected via the sacral hiatus into the cerebrospinal fluid to produce total spinal anesthesia (paralysis of all four limbs). Total spinal anesthesia failed to prevent the occurrence or attenuate the course of MH in swine given halothane, 1 per cent (five pigs) or halothane and succinylcholine, 3 mg/kg (one pig). Total spinal anesthesia did prevent the expected increases in norepinephrine and epinephrine during MH in all six swine. Since dantrolene is specifically therapeutic in MH, its effect on the sympathetic response to stress was measured in two other susceptible swine. Treatment with dantrolene, 10 mg/kg, intravenously, did not prevent increases in catecholamines due to stress caused by either respiratory and metabolic acidosis (Paco2 110 torr, base excess −20) combined or hemorrhagic hypotension (mean pressure 40 torr). The authors conclude that the sympathetic nervous system is involved in porcine MH only as a secondary response to stress; that conduction anesthesia will not protect pigs from MH; and that the efficacy of dantrolene in porcine MH is due to its effects on skeletal muscle rather than to depression of the sympathetic nervous system.
Journal Article•
TL;DR: Propranolol completely blocked the rise in cAMP observed following incubation of cells with epinephrine, norepinephrine, or phenylephrine; yet an increase in phosphorylase a activity and a decrease in synthase I activity were still observed.
Abstract: The effects of alpha and beta adrenergic agonists and antagonists on the percentages of phosphorylase a and glycogen synthase I activities were investigated in isolated rat adipocytes. (-)-Epinephrine, (-)-norepinephrine, and (-)-isoproterenol increased the concentration of adenosine cyclic 39,59-monophosphate (cAMP) and the percentage of phosphorylase a activity in a dose-dependent manner. Isoproterenol was about 10 times more potent than epinephrine or norepinephrine with respect to these increases as well as to decreases in the percentage of glycogen synthase I activity. Although all three agents decreased synthase I activity to the same extent, the maximal effects of epinephrine and norepinephrine on phosphorylase a activity were approximately 25% greater than the maximal effect of isoproterenol. In the presence of the alpha adrenergic antagonists phentolamine, phenoxybenzamine, and dihydroergotamine, the maximal effect of norepinephrine on increasing the percentage of phosphorylase a was reduced to that of isoproterenol. All three alpha adrenergic antagonists potentiated the ability of norepinephrine to increase the concentration of cAMP. The maximal effect of (-)-phenylephrine on phosphorylase a activity was less than the maximal effect of isoproterenol. When cells were incubated with isoproterenol plus phenylephrine, phosphorylase a activity was increased to levels observed with epinephrine or norepinephrine. Methoxamine also increased phosphorylase a activity, and the effects of isoproterenol and methoxamine on phosphorylase were additive. Incubation of cells with 5 mM dibutyryl cAMP decreased synthase I activity and increased phosphorylase a activity to the level observed with isoproterenol. When dibutyryl cAMP was added to cells together with isoproterenol or epinephrine, no further increase in phosphorylase a activity over that obtained with the catecholamines alone was observed. However, when cells were incubated with phenylephrine plus dibutyryl cAMP, the percentage of phosphorylase a activity was increased to that observed with epinephrine. (-)-Propranolol completely blocked the rise in cAMP observed following incubation of cells with epinephrine, norepinephrine, or phenylephrine; yet an increase in phosphorylase a activity and a decrease in synthase I activity were still observed. Incubation of cells with 20 µM propranolol together with 1 µM phenoxybenzamine did not reverse the decrease in synthase I activity produced by 200 milliunits/ml of adrenocorticotrophic hormone, but completely abolished the effect of 200 µM phenylephrine. Incubation of cells with methoxamine (1-10 µM) decreased glycogen synthase I activity. Phentolamine (20 µM) completely blocked this effect of methoxamine, as well as the ability of methoxamine to increase phosphorylase a activity.
TL;DR: Results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrh rhythmogenicity of epinphrine.
Abstract: The purpose of this study was to examine the effects of pharmacologic alterations of adrenergic terminating mechanisms by cocaine, tropolone, aminophylline, and ketamine on the ability of epinephrine to induce arrhythmias during halothane-nitrous oxide anesthesia in dogs. Because the first three drugs inhibit intraneuronal uptake of catecholamines, extraneuronal catechol-O-methyl transferase (COMT), and phosphodiesterase, respectively, they might be expected to potentiate epinephrine-induced arrhythmias. To evaluate this possibility, the authors devised a technique for determining the minimal arrhythmic dosage of epinephrine that permitted graded assessment of changes in the sensitivity of the heart to epinephrine-induced arrhythmias. When the first three drugs were administered to the same dog in the order listed at intervals of 60 minutes, they sequentially increased the ability of epinephrine to induce arrhythmias. Ketamine, according to several investigators, also appears to block reuptake of catecholamines, and when studied was also found to enhance the arrhythmogenicity of epinephrine. The extent of enhancement was comparable to that seen with cocaine. These results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrhythmogenicity of epinephrine.
TL;DR: The data indicate that sensitization with antigen may change the biological properties of the organism, as evidenced by the increased outflow of PGs and histamine in sensitized and anaphylactic lungs.
TL;DR: The results add to the probability that hormone sensitivity of membrane-bound adenylyl cyclase activity is regulated in part by endogenous factors.
TL;DR: It is concluded that the decrease in catecholamine secretion caused by enflurane is in part due to a direct effect on the chromaffin cell, namely to an inhibition of the secretion-stimulating effect of acetylcholine released from splanchnic nerves.
Abstract: The effects of enflurane anesthesia on adrenal medullary catecholamine secretion and on the pressor effect of splanchnic-nerve stimulation were studied in cats given pentobarbital for basal anesthesia. Inhalation of enflurane, 1.2 and 2.2 per cent, caused dose-related inhibition of both spontaneous catecholamine release and secretion evoked by splanchnic-nerve stimulation. During inhalation of 2.2 per cent enflurane spontaneous release of epinephrine was decreased to 19 and 25 per cent, respectively, of the initial values, and the stimulated release was decreased to 30 and 15 per cent, respectively. Enflurane also inhibited the pressor effect of splanchnic-nerve stimulation, whereas that of norepinephrine was not changed significantly. These results are similar to those previously obtained with halothane and methoxyflurane. It is concluded that the decrease in catecholamine secretion caused by enflurane is in part due to a direct effect on the chromaffin cell, namely to an inhibition of the secretion-stimulating effect of acetylcholine released from splanchnic nerves.
TL;DR: The authors conclude that the increase in epinephrine level (stress response of the organism) is the direct cause of the observed changes in uterine motility.
TL;DR: It is concluded that stimulation of the platelet adrenergic receptors may either result in promotion (alpha-stimulation) or inhibition (beta- Stimulation) of platelet aggregation and differences in the ratios or responses of alpha/beta receptors may account for species variations in the Platelet aggregation response to catecholamine challenge.
Abstract: Epinephrine, known to potentiate and elicit aggregation of human platelets, was shown to inhibit thrombin-induced aggregation of rat platelets, delaying the onset of aggregation from 2 to 12 times. Incubation of rat platelet suspensions with propranolol (1.25--30 micrometer), inactive by itself, totally prevented the inhibitory effect of epinephrine and also permitted a potentiation effect to show up. On the contrary, phentolamine (1.25--30 micrometer) potentiated the inhibitory effect of epinephrine on rat platelets and unmasked an inhibitory effect on human platelets. Finally, isoproterenol (0.25--9 micrometer) produced a marked inhibition of aggregation induced by thrombin, ADP and collagen in the three species studied, but most particularly in the rat. From these results, we conclude that stimulation of the platelet adrenergic receptors may either result in promotion (alpha-stimulation) or inhibition (beta-stimulation) of platelet aggregation. Furthermore, differences in the ratios or responses of alpha/beta receptors may account for species variations in the platelet aggregation response to catecholamine challenge.
TL;DR: Comparison of the bronchodilator and cardiovascular effects of subcutaneous terbutaline and epinephrine in the treatment of acute asthmatic attacks in children disclosed thatBronchodilation occurred with 5 min after sub cutaneous injection of either drug.
Abstract: Comparison of the bronchodilator and cardiovascular effects of subcutaneous terbutaline and epinephrine in the treatment of acute asthmatic attacks in children disclosed that bronchodilation occurred with 5 min after subcutaneous injection of either drug (0.01 mg/kg, maximum 0.25 mg). Bronchodilation was maintained for 4 hr after administration of either drug. Small increases in pulse rate followed administration of terbutaline but not epinephrine. No clinically significant side effects were noted with either drug.
TL;DR: It is suggested that, in epinephrine-treated rats, blood glucose was converted to blood lactate predominantly while muscle glycogen selectively yielded the metabolites other thanBlood lactate, which suggests compartmentalization of glycolytic pathway in the peripheral tissues of epinphrine- treated rats.
Abstract: The effect of epinephrine on Cori cycle activity has been studied by a tracer kinetic technique. The subcutaneous injection of epinephrine into fasted adrenodemedullated rats activated gluconeogenesis and increased glucose utilization. Most of the glucose utilized in epinephrine-treated rats was converted to lactate, and the conversion to the metabolites other than lactate was markedly suppressed by epinephrine. As a result, not only hyperglycemia and hyperlactacidemia developed, but also the contribution of the Cori cycle to glucose metabolism increased after epinephrine. The glucose-alanine cycle, which is roughly one-third as active as the Cori cycle, was only slightly activated by epinephrine. No evidence was obtained, in vivo and in vitro, for the increased formation of lactate from muscle glycogen which decomposed in response to epinephrine. It is suggested that, in epinephrine-treated rats, blood glucose was converted to blood lactate predominantly while muscle glycogen selectively yielded the metabolites other than blood lactate. This suggests compartmentalization of glycolytic pathway in the peripheral tissues of epinephrine-treated rats.
TL;DR: Liver cells were obtained from adult rats by a collagenase perfusion technique and cultured as monolayers in serum-free media and cells became refractory to further stimulation of cAMP levels by epinephrine.
Abstract: Liver cells were obtained from adult rats by a collagenase perfusion technique and cultured as monolayers in serum-free media. Epinephrine and isoproterenol both induced large increases in intracellular adenosine 3':5'-monophosphate (cAMP) within 1-2 min whereas epinephrine (but not isoproterenol) induced 2- to 3-fold increases in the rate of alpha-aminoisobutyric acid transport within 2-4 hr after a 1 hr lag. Propranolol abolished the increase in cAMP elicited by epinephrine and isoproterenol, but did not block the induction of alpha-aminoisobutyric acid transport by epinephrine. In contrast, dihydroergotamine abolished and phentolamine diminished the induction of alpha-aminoisobutyric acid transport by epinephrine but did not decrease the stimulation of cAMP levels by epinephrine. Epinephrine dose response curves for cAMP and alpha-aminoisobutyric acid transport were similar. Once exposed to epinephrine, cells became refractory to further stimulation of cAMP levels by epinephrine.