Showing papers on "Epinephrine published in 1969"
Journal Article•
TL;DR: It may be that, although mediated by different types of receptor, epinephrine exerts an effect on the coupling of excitation and transmitter release in nerve which is analogous to its action on excitation-contraction coupling in muscle, both effects involving changes in the levels of free calcium ions.
Abstract: Epinephrine exerts a direct action on mammalian muscle fibers which is mediated via β-receptors. Activation of these receptors results in prolongation of the active state of white, fast-contracting muscles and curtailment of the active state of red, slow-contracting muscles. In chronically denervated mammalian muscles of both types, and in chronically denervated avian muscles, activation of the β-receptors increases the fibrillary discharge and the tone exerted by the muscles. It is suggested that these effects on muscle contractility may arise through activation of the adenyl cyclase/cyclic 3' ,5'-AMP system, which in turn leads to changes in the rates of uptake of Ca2+ by the sarcoplasmic reticulum. Activation of the β-receptors also increases the muscle demarcation potential, presumably as a result of hyperpolarization of the muscle fiber membranes. Under sensitive conditions, this effect can be shown to lead to a depressant effect on neuromuscular transmission.
Epinephrine also exerts an initial faciitatory action on neuromuscular transmission in all types of muscle, and this is mediated via α-receptors, probably located in the motor nerve endings, activation of which appears to cause an inincrease in the amount of acetylcholine released by the nerve impulse. Hyperpolarization of motor nerve endings increases release of transmitter by nerve impulses, and epinephrine may act by hyperpolarizing some part of the terminal membrane. It may be that, although mediated by different types of receptor, epinephrine exerts an effect on the coupling of excitation and transmitter release in nerve which is analogous to its action on excitation-contraction coupling in muscle, both effects involving changes in the levels of free calcium ions. Cyclic 3' ,5'-AMP may also be a mediator in the facilitatory effect on neuromuscular transmission, and this fact implies the unusual situation that, in nerve, increased levels of the nucleotide may be evoked through α-receptors.
The defatiguing action of epinephrine and sympathetic stimulation in mammalian fast-contracting muscles mainly involves the prejunctional α-receptors, but the postjunctional β-receptors also contribute. In fatigued frog muscle, only prejunctional α-receptors are involved. Apart from an indirect action arising from circulatory changes, epinephrine is without a defatiguing effect in red, slow-contracting mammalian muscles.
A consideration of the effective doses of catecholamines suggests that only the action of epinephrine on the sensitive slow-contracting red muscle fibers has any physiological significance. This action is probably responsible for the enhancement of physiological tremor and of Parkinsonian tremor produced by catecholamines in man, and for the tremor often associated with phaeochromocytoma.
274 citations
TL;DR: It is concluded that hydrocortisone enhances the responses of vascular smooth muscle to epinephrine and norepinephrine by inhibiting a major enzymatic pathway for the inactivation of these amines.
Abstract: Hydrocortisone potentiated responses of rabbit aortic strips to catecholamines (epinephrine, norepinephrine, nordefrin, isoproterenol) but not to amines lacking the catechol nucleus (phenylephrine, synephrine, methoxamine). Contractions in response to epinephrine were increased much more than those to norepinephrine. Neither the presence of cocaine nor pretreatment of the rabbits with reserpine impaired the potentiating action of hydrocortisone. Experiments with the oil immersion technique (to prevent loss of amine by diffusion from the tissue) demonstrated that hydrocortisone reduced the rate at which aortic strips inactivated epinephrine, apparently by inhibiting catechol-O-methyl transferase (COMT). Known inhibitors of COMT (U-0521, tropolone, pyrogallol) potentiated responses of aortic strips to epinephrine much more than to norepinephrine and also enhanced responses to isoproterenol and nordefrin to the same extent as did hydrocortisone. Known inhibitors of COMT consistently abolished the enhancing effects of hydrocortisone without materially interfering with potentiation produced by cocaine which is mediated through an independent mechanism unrelated to amine inactivation. Hydrocortisone also abolished the enhancing effects of known COMT inhibitors. It is concluded that hydrocortisone enhances the responses of vascular smooth muscle to epinephrine and norepinephrine by inhibiting a major enzymatic pathway for the inactivation of these amines.
209 citations
TL;DR: Findings are consistent with the hypotheses that the positive inotropic effects of epinephrine and glucagon may occur as a result of an augmentation of the sarcotubular calcium pool(s) and this effect is mediated, at least in part, by an elevation of cyclic 39, 59-AMP levels produced by activation of an adenyl cyclase localized to the sarcoplasmic reticulum.
Abstract: The mechanisms by which the catecholamines and glucagon increase myocardial contractility were investigated by studying the effects of cyclic 39, 59-AMP, epinephrine, and glucagon on calcium accumulation by a microsomal fraction of canine myocardium thought to represent sarcoplasmic reticulum, and by assaying the microsomal fraction for adenyl cyclase activity. Each agent produced a concentration-dependent increase in calcium accumulation. Moreover, adenyl cyclase, an enzyme activated by epinephrine and glucagon and responsible for the production of cyclic 39, 59-AMP, was present in the microsomal fraction. Its specific activity and responsiveness to epinephrine and glucagon were similar to that previously found in sarcolemmic fractions. The beta-receptor blocking agent propranolol abolished the activation of adenyl cyclase and increase in microsomal calcium accumulation produced by epinephrine, but was without effect when these same changes were produced by glucagon. These findings are consistent with the hypotheses that: (1) the positive inotropic effects of epinephrine and glucagon may occur as a result of an augmentation of the sarcotubular calcium pool(s); and (2) this effect is mediated, at least in part, by an elevation of cyclic 39, 59-AMP levels produced by activation of an adenyl cyclase localized to the sarcoplasmic reticulum.
194 citations
TL;DR: The mean peak excretion of both noradrenaline and adrenaline was significantly greater in the 9 patients who died than in the 46 patients who survived, and the mean level of catecholamine excretion in the first week after infarction was also significantly greater.
174 citations
TL;DR: It is postulated that the catecholamine release which is stimulated by volume depletion, infection, or stress may be an important "reversible" factor in some patients with diabetic ketoacidosis.
Abstract: This review summarizes evidence showing inhibition of insulin release by epinephrine and norepinephrine. The receptor theory for catecholamine action is discussed and the inhibition shown to be mediated by α-adrenergic receptor stimulation; β-adrenergic receptors are also described which stimulate insulin release, indicating a unique dual receptor system in the pancreatic islet. The possible physiologic importance of these findings is suggested in a discussion of the carbohydrate intolerance found in patients with pheochromocytoma and during severe hypothermia in children. A possible relation of the inhibition of insulin release and the increased fatty acid mobilization caused by catecholamines to exacerbations of the diabetic syndrome is examined. It is postulated that the catecholamine release which is stimulated by volume depletion, infection, or stress may be an important "reversible" factor in some patients with diabetic ketoacidosis.
142 citations
TL;DR: Urine and tumor catecholamine levels were elevated and showed a predominance of epinephrine secretion over that of norepinephrine in a patient with pheochromocytoma, and the use of adrenergic blocking agents in these patients is discussed.
116 citations
TL;DR: An adrenocorticotropic hormone (ACTH)-sensitive, steroid-producing mouse adrenal tumor was homogenized and fractionated by differential centrifugation and adenyl cyclase activity that was stimulated by ACTH and by fluoride was purified 10- to 20-fold and localized to particulate fractions.
112 citations
TL;DR: The results suggest that the effect of insulin on glycogen transferase activity in skeletal muscle does not depend upon changes in the tissue concentration of cyclic AMP.
108 citations
TL;DR: The results show that in the membrane of the fat cell a single catalytic unit of adenyl cyclase is coupled to distinctive selectivity sites for three lipolytic hormones.
Abstract: A large number of hormones, of diverse molecular structure, evoke characteristic responses in target cells via the intermediary 3′,5′-AMP, the specificity of hormone action upon cell type being achieved by selective stimulation of adenyl cyclase. In the fat cells of rat adipose tissue, adenyl cyclase is stimulated by a number of hormones of disparate molecular structure, posing the question whether this cell type posesses multiple cyclase systems with distinctive specificities for individual hormones, or a single cyclase with broad specificity to a variety of hormones.
Studies of the stimulatory effects of adenocorticotropin, glucagon, and epinephrine upon the adenyl cyclase of the rat fat cell “ghosts” (plasma membrane sacs) have shown that distinctive selectivity sites for each of these hormones can be differentiated. The β-adrenergic blocking agent Ko 592 abolished the stimulatory effect of epinephrine without influencing adenocorticotropin or glucagon; Ca was required for adenocorticotropin action, but not for glucagon or epinephrine. Dose-response curves show that the affinity of hormones to the cyclase system was in the order: glucagon > adenocorticotropin ≫ epinephrine; the magnitude of cyclase activation by maximal doses of hormones had a reversed order. Combinations of maximal doses of hormones failed to produce additive stimulation. The results show that in the membrane of the fat cell a single catalytic unit of adenyl cyclase is coupled to distinctive selectivity sites for three lipolytic hormones.
101 citations
Journal Article•
TL;DR: The epinephrine-forming enzyme phenylethanolamine-N-methyl transferase (PNMT) can be demonstrated in various brain regions of the rat, cat, hen and turtle.
Abstract: Epinephrine forming enzyme phenylethanolamine-N- methyl transferase /PNMT/ in various brain regions of rats, cats, hens and turtles
97 citations
TL;DR: Catecholamine reductions, due only in part to dilutional hypertrophy, may be related to increased utilization and may serve to enhance synthesis of the neurotransmitter and maintain the increase in blood pressure.
Abstract: Norepinephrine synthesis was determined in the heart and adrenals of rabbits made hypertensive by complete denervation of the carotid sinuses and aortic arch. There was a 24% reduction of norepinephrine concentration in the left ventricle 3 weeks after denervation, despite evidence of enhanced synthesis as determined by three methods: (1) an 18% increase in apparent synthesis rates (from 0.76 to 0.90 mµmoles/g/hour) calculated from norepinephrine turnover rates after infusion of DL-norepinephrine-3H; (2) a 124% increase in synthesis rates (from 2.1 to 4.7 mµmoles/g/hour) estimated from the incorporation of label from infused tyrosine-3H; (3) a 50% increase (from 4.0 to 6.0 mµmoles/g/hour) in the activity of the regulatory enzyme tyrosine hydroxylase. Additionally, in the denervated rabbits there was a 43% reduction in the amount of epinephrine in the adrenal gland 2 days after denervation and a return to normal values at 3 weeks. Adrenal tyrosine hydroxylase, phenylethanolamine-N-methyl transferase, and t...
TL;DR: Beta adrenergic blockade prior to a repeat stress interview blocked the metabolic changes without interfering with the hormonal response to stress, and the need for hospitalization for each of these children has been markedly decreased.
TL;DR: Evidence is provided in support of the hypothesis that the physiologic and biochemical effects of interstitial cell stimulating hormone and follicle stimulating hormone in testis and probably in ovary are mediated through adenosine 3′,5′-monophosphate.
TL;DR: The results indicate that epinephrine binds to a receptor protein rather than interacting directly with the enzyme adenyl cyclase, which is shown to be specifically localized in the plasma membrane of rat liver.
TL;DR: It is suggested that the sympathetic control of gastrointestinal tone and motility is exerted through two different routes: inhibition of intramural cholinergic plexuses and direct relaxation of smooth muscle cells.
Abstract: 1. In isolated guinea-pig terminal colon, the effect of sympathetic stimulation on contraction and acetylcholine release elicited by pelvic and transmural stimulation was investigated.
2. Sympathetic stimulation reduced the nerve-mediated contractile responses more than those produced by added acetylcholine.
3. Sympathetic stimulation also reduced the acetylcholine released during pelvic and transmural stimulation at low frequency. The inhibitory effect on acetylcholine released from resting colons is concealed by the simultaneous release of acetylcholine in considerable amounts from stimulated periarterial nerves which probably contain parasympathetic fibres.
4. The inhibitory effect of endogenous and exogenous catecholamines prevails when cholinergic neurones fire at low rates. It was confirmed that adrenaline is more active than noradrenaline.
5. The release of acetylcholine from unstimulated colons was for the most part maintained by nerve-conducted activity, because tetrodotoxin was able to reduce it to about one-tenth.
6. It is suggested that the sympathetic control of gastrointestinal tone and motility is exerted through two different routes: inhibition of intramural cholinergic plexuses and direct relaxation of smooth muscle cells.
7. The possible site and mechanism of action of catecholamines on intramural cholinergic structures is briefly discussed.
Journal Article•
TL;DR: LB 46 appears to be one of the most potent beta adrenergic blocking drugs so far known and one ofThe least effective in depressing myocardial function.
Abstract: The beta adrenergic blocking effects, the antiarrhythmic properties and the local anesthetic activity of LB 46 have been investigated. In chloralose-anesthetized dogs, LB 46 was 10-to 40-fold more potent than propranolol in antagonizing the cardiovascular effects of isoproterenol and the cardiac stimulating effects of epinephrine, norepinephrine and right stellate ganglion stimulation. In isolated preparations, LB 46 was 3-to 10-fold more potent than propranolol. At beta adrenergic blocking doses, LB 46 was devoid of any intrinsic beta sympathomimetic activity. Furthermore, no modification of the resting cardiovascular parameters of the anesthetized dog could be detected. LB 46 at doses 60-fold higher than the beta adrenergic blocking doses reversed ouabain-induced ventricular tachycardia in dogs, but reversion was then associated with moderate cardiac depressant effects. This reversion occurred although LB 46 had very weak local anesthetic properties. LB 46 appears to be one of the most potent beta adrenergic blocking drugs so far known and one of the least effective in depressing myocardial function.
Journal Article•
TL;DR: The effects of combinations of inhibitors indicated that catechol-O-methyltransferase and monoamine oxidase function in series, with the latter an effective alternate mechanism for the inactivation of norepinephrine and somewhat less effective for epinephrine.
Abstract: Experiments with the oil-immersion technique demonstrated that Omethylation is the primary enzymatic mechanism for the inactivation of a low concentration (1x10-8) of both norepinephrine and epinephrine in rabbit aortic strips, but inhibition of catechol-O-methyltransferase slowed the rate of inactivation of norepinephrine considerably less than it did that of epinephrine. Inhibition of monoamine oxidase had a negligible effect on the inactivation of either, if catechol-O-methyltransferase activity was unimpaired. The effects of combinations of inhibitors indicated that catechol-O-methyltransferase and monoamine oxidase function in series, with the latter an effective alternate mechanism for the inactivation of norepinephrine and somewhat less effective for epinephrine. A possible anatomical basis for this behavior is pointed out. Experiments with a 100 -fold higher concentration of these catecholamines showed that the major intrinsic pathways of inactivation are deamination and O-methylation for norepinephrine and epinephrine, respectively. It is suggested that the high concentration of agonist swamped the normal, organized system of inactivation, with a more or less simultaneous presentation of amine to both enzymes, which revealed their capacities for handling the two catecholamines. The contributions of binding and storage mechanisms to norepinephrine and epinephrine inactivation were assessed on the basis of the effects of cocaine. These processes were found to be considerably less important than enzymatic pathways in the inactivation of physiologic concentrations of norepinephrine and epinephrine and were found to make only a minor contribution to the inactivation of high concentrations.
TL;DR: Epinephrine infusions inhibited the insulin secretory response to the short-chain fatty acids propionate and butyrate and completely abolished the plasma growth hormone response to arginine infusions, indicating that the capacity of the ruminant to respond to shortchain fa...
Abstract: Epinephrine infusions (0.5–1.0 μg/kg/min) inhibited the insulin secretory response to the short-chain fatty acids propionate (0.5 mmole/kg) and butyrate (0.5 mmole/kg) and intravenous arginine (12.5 g). This inhibitory effect of epinephrine was blocked by alpha adrenergic receptor blockade (i.e., phentolamine) but not by beta adrenergic receptor blockade (i.e., propranolol). Epinephrine also completely abolished the plasma growth hormone response to arginine infusions. This effect was not altered by alpha adrenergic receptor blockade sufficient to reverse the inhibitory effect of epinephrine on insulin secretion. A significant increase (i.e., 5- to 10-fold) in plasma growth hormone was consistently noted 30–60 min after stopping the infusion of epinephrine. Short-chain fatty acids were demonstrated to stimulate insulin secretion in the newborn lamb, which at birth is monogastric and does not have a functioning forestomach. This result indicates that the capacity of the ruminant to respond to shortchain fa...
TL;DR: It is proposed that adrenal corticosteroids have a role in maintaining physiological phosphorylase levels and in the conversion of inactive to active phosphory lase, possibly at the level of the phosphoryLase kinase kinases reaction.
TL;DR: Constant intravenous infusion of glucose is the method of choice for the treatment of patients with acute congestive cardiac failure and hypoglycemia rather than epinephrine or glucagon.
Abstract: Acute congestive cardiac failure and hypoglycemia were observed simultaneously in 27 patients with underlying heart disease. Seventeen of this group had the hypoplastic left heart syndrome, two had transposition of the great vessels, and four had hypoglycemia postoperatively. Liver biopsy in four patients revealed a marked reduction of hepatic glycogen both biochemically and electron microscopically but normal phosphorylase and glucose-6-phosphatase activity. Reduction of their dietary intake and gastrointestinal malabsorption caused by congestive cardiac failure are suggested as possible mechanisms for the observed hepatic glycogen depletion. Constant intravenous infusion of glucose is the method of choice for the treatment of patients with acute congestive cardiac failure and hypoglycemia rather than epinephrine or glucagon. Five patients recovered sufficiently following treatment of hypoglycemia and acute cardiac failure to be discharged from the hospital.
TL;DR: Granular gland secretion in response to catecholamines is apparently mediated by muscle contraction resulting from α-adrenergic stimulation.
TL;DR: Hypertensive crisis developed unexpectedly during removal of an adrenal tumor in a patient with Cushing's syndrome, and the patient required only adrenal cortical replacement therapy postoperatively.
TL;DR: It is suggested that the adenyl cyclase system for the synthesis of adenosine 3',5'-cyclic monophosphate in adipocytes contains at least two different types of activation receptor sites for hormones, and that PGE1 binds to only one type of site while the β-adrenergic blockers are effective against both types.
TL;DR: It is concluded that epinephrine and dibutyryl cyclic AMP stimulate protein synthesis directly and independently of their effect on secretory activity.
TL;DR: In this article, the levels of plasma free fatty acids, urinary epinephrine, norepinephrine, and vanyllylmandelic acid were measured in six young male students with perennial, mild to moderate asthma in remission, and six matched healthy controls, on successive days under conditions of "stress" (exposure to mental arithmetic and a film) and "relaxation," demonstrated significant biochemical differences although both groups were equally aroused emotionally.
Abstract: Plasma free fatty acids, urinary epinephrine, norepinephrine and vanyllylmandelic acid, measured in six young male students with perennial, mild to moderate asthma in remission, and six matched healthy controls, on successive days under conditions of "stress" (exposure to mental arithmetic and a film) and "relaxation," demonstrated significant biochemical differences although both groups were equally aroused emotionally. The control subjects showed a marked mobilization of free fatty acids and marked rise in urinary epinephrine under stress, whereas the patients had low and relatively constant levels for both substances under both conditions. In contrast, norepinephrine and vanyllylmandelic acid did not differentiate between the two groups. These findings are consistent with the hypothesis that there is decreased activity of the adrenal medulla but normal activity of the sympathetic nervous system in bronchial asthma.
TL;DR: It is proposed that adrenal corticosteroids play a role in the conversion of inactive to active phosphorylase and in the regulation of phosphoryLase synthesis.
TL;DR: It has been suggested that the differences during fasting between gravid and nongravid rats may be ascribed to the greater homeostatic challenge that is posed by starvation in late pregnancy, and by the hypoglycemia that may occur under these circumstances.
Abstract: Twenty-four hr urinary excretions of catecholamines did not differ in pregnant, post partum and age-matched virgin rats when they were given unrestricted access to food. Significant differences became manifest when food was withheld: Fasting from day 19–21 of gestation elicited significant increases in urinary epinephrine on each of the 2 days and increased urinary norepinephrine on the second. Contrariwise, urinary catecholamines were not increased when the same animals were fasted again on day 10–12 post partum or when agematched virgin rats were subjected to comparable dietary deprivation. It has been suggested that the differences during fasting between gravid and nongravid rats may be ascribed to the greater homeostatic challenge that is posed by starvation in late pregnancy, and by the hypoglycemia that may occur under these circumstances. The potential contributions of enhanced sympathoadrenal activity to the metabolic response to starvation during gestation have been discussed. (Endocrinology 84: ...
TL;DR: It was found that mitotic activity was observed only under those conditions where activity of β-adrenergic receptors could be implicated (ISO, PC, and UR), and the β-blocking agent, Inderal, was used to demonstrate this point.
Abstract: SummaryA series of sympathomimetic and parasympathomimetic agents were administered chronically to rats. At 3 and 10 days, the effects of these agents [the β-adrenergic drug, ISO; the primarily α-adrenergic drugs, epinephrine and phenylephrine, and the parasympathomimetic agents, pilocarpine (PC) and Urecholine (UR)] on parotid gland weight, and size and mitotic activity of acinar cells were examined. It was found that mitotic activity was observed only under those conditions where activity of β-adrenergic receptors could be implicated (ISO, PC, and UR), and the β-blocking agent, Inderal, was used to demonstrate this point. Increases in cell and gland size more generally accompanied β-adrenergic activity and were evident even in the absence of a distinct mitotic response; α-mediated effects, however, produced no mitotic effects but instead decreased cell and gland size. Secretory activity was not necessarily involved in any of the β-adrenergically mediated increases in gland size, acinar cell size or number.
TL;DR: It is concluded that both α and β adrenergic receptors are present in the hepatic arterial bed, however, β receptor responses may be difficult to elicit if the basal tone of the vascular bed is already reduced by prior procedures.
Abstract: The hepatic arterial blood flow of cats anesthetized with pentobarbital was recorded with an electromagnetic flowmeter. Administration of isoprenaline by close arterial infusion caused a vasodilatation which was blocked after propranolol. Adrenaline caused a variable change but after propranolol it consistently produced vasoconstriction, and after phenoxybenzamine, vasodilatation. One hour after phenoxybenzamine, stimulation of the sympathetic nerves caused a marked vasodilatation which was blocked by propranolol. It is concluded that both α and β adrenergic receptors are present in the hepatic arterial bed. However, β receptor responses may be difficult to elicit if the basal tone of the vascular bed is already reduced by prior procedures.
Journal Article•
TL;DR: Results are consistent with the view that the medial muscle has a denser adrenergic innervation than the inferior muscle and are proposed that this difference is causally related to the fact that the innervated medial muscle is significantly less sensitive to l -norepinephrine and l -epinephrine than the Innervated inferior muscle.
Abstract: The medial smooth muscle of the cat9s nictitating membrane contains about twice the amount of endogenous norepinephrine found in the inferior muscle. In relation to its weight, the medial muscle takes up and retains about twice the amount of norepinephrine-H 3 recovered from the inferior muscle; however, in relation to the content of endogenous norepinephrine, uptake is equal for both muscles. These results are consistent with the view that the medial muscle has a denser adrenergic innervation than the inferior muscle. It is proposed that this difference is causally related to the fact that the innervated medial muscle is significantly less sensitive to l -norepinephrine and l -epinephrine than the innervated inferior muscle. The differences in sensitivity disappear after denervation. Apparently the density of adrenergic innervation is one of the factors which influence the concentration of certain amines at the receptors of effector organs.