Showing papers on "Epinephrine published in 1968"
TL;DR: In combination, epinephrine and caffeine acted synergistically, producing large increases in cyclic AMP, indicating that, as in other systems, the catecholamines act to stimulate adenyl cyclase and the methyl xanthines act to inhibit the cyclic nucleotide phosphodiesterase.
533 citations
TL;DR: There appears now to be no reasonable doubt that both epinephrine and norepinephrine belong to the category of hormones which are responsive to psychological influences and catecholamine levels, furthermore, appear sensitively to reflect relatively common, psychological reactions associated with “everyday” events, tasks, and activities.
Abstract: There appears now to be no reasonable doubt that both epinephrine and norepinephrine belong to the category of hormones which are responsive to psychological influences.Catecholamine levels, furthermore, appear sensitively to reflect relatively common, psychological reactions associated with “everyd
313 citations
TL;DR: Intensely fluorescent, terminal varicosities were observed within large preterminal nerve trunks only in the youngest animals, suggesting that the sympathetic nerves move into, rather than form within, the heart.
Abstract: The sympathetic innervation of the rabbit heart, as a function of age, was studied by measuring the cardiac concentration of catecholamines and observing the anatomic distribution of sympathetic nerves by the monoamine fluorescense technique. The cardiac concentration of norepinephrine in late gestation was quite low; the levels rose progressively after birth to reach adult levels by about three weeks of age. Similar small amounts of epinephrine were found in the hearts at all ages. Substantially less change in adrenal catecholamines accompanied advancing age. At all ages a close correlation was noted between the norepinephrine levels and the histochemical demonstration of sympathetic innervation. Intensely fluorescent, terminal varicosities were observed within large preterminal nerve trunks only in the youngest animals, suggesting that the sympathetic nerves move into, rather than form within, the heart. Chromaffin cells were observed in the hearts at all ages.
213 citations
TL;DR: In resuscitating dogs subjected to ten minutes of circulatory arrest due to ventricular fibrillation, a number of drugs were used with artificial ventilation of the lungs, external cardiac massage, and external electrical counter-shock.
Abstract: In resuscitating dogs subjected to ten minutes of circulatory arrest due to ventricular fibrillation, a number of drugs were used with artificial ventilation of the lungs, external cardiac massage, and external electrical counter-shock. Resuscitation was more successful when epinephrine was used than when no drug therapy or sodium bicarbonate were used. Combination of lidocaine with epinephrine increased the frequency of defibrillation, but circulation was not restored more often than with epinephrine alone. The use of methoxamine hydrochloride was followed by successful resuscitation more often than was the use of epinephrine. Combination of epinephrine and sodium bicarbonate was as effective as methoxamine in restoring circulation, and inspection of the survivors after 24 hours suggested that the combination might be preferable.
190 citations
TL;DR: The beta -adrenergic agonist, isoproterenol, evoked hyperthermia but no feeding, and hence alpha and beta adrenergic functions in the central nervous system may be distinguished.
182 citations
Journal Article•
TL;DR: The results of these studies indicate that adenyl cyclase of rat pineal responds to specific adrenergic and adrenolytic drugs in a manner similar to that of a postjunctional beta adrenergic receptor.
Abstract: Adenyl cyclase activity of rat pineal gland homogenates was assayed in vitro by measuring the rate of formation of radioactive cyclic 39, 59-adenosine monophosphate (cyclic 39, 59-AMP) from its C 14 -labeled precursor, adenosine triphosphate. Enzyme activity was increased up to 3-fold by the addition of l -norepinephrine. Cyclic 39, 59-AMP formation was also enhanced by l -epinephrine and l -isoproterenol, but not by d -norepinephrine, dl -dihydroxymandelic acid, dl -normetanephrine, dopamine, tyramine, d -amphetamine or l -phenylephrine. Serotonin and histamine, which are present in the pineal gland and have been shown to increase cyclic 39, 59-AMP formation in other tissues, did not stimulate pineal adenyl cyclase. Similarly, the polypeptides, glucagon, adrenocorticotropic hormone and luteinizing hormone, which enhance the accumulation of the cyclic nucleotide in liver, adrenal cortex and corpus luteum, respectively, failed to stimulate adenyl cyclase of the pineal. Drugs such as guanethidine, cocaine and desmethylimipramine, which alter sympathetic responses by an action at adrenergic nerve endings, also failed to influence pineal adenyl cyclase activity. On the other hand, the beta adrenergic blocking agents, propranolol and dichloroisoproterenol, which affect beta adrenergic receptors, antagonized the norepinephrine-induced stimulation of enzyme activity. The alpha blockers, phenoxybenzamine and phentolamine, were considerably less effective in this regard. Thus, the results of these studies indicate that adenyl cyclase of rat pineal responds to specific adrenergic and adrenolytic drugs in a manner similar to that of a postjunctional beta adrenergic receptor.
149 citations
Journal Article•
TL;DR: The two necessary criteria for an alpha -receptor mediated response have been fulfilled and a positive inotropic effect has been shown to be blocked specifically by alpha blocking agents, and the ability of epinephrine anti norepinephrine to produce the effect-has been shows to be greater than that of isoproterenol.
Abstract: The question of the role of myocardial alpha adrenergic receptors in the inotropic effects of sympathomimetic agents has been considered. Phenylephrine was found to produce a two-component positive inotropic effect in guinea-pig atria. The positive inotropic effect of phenylephrine in concentrations up to l0-6 M was specifically blocked by phentolamine or phenoxybenzamine but not by pronethalol. At higher concentrations of phenylephrine, a second component of activity appeared which was blocked by pronethalol. A portion of the positive inotropic response to epinephrine and norepinephrine was also shown to be blocked by phentolamine or phenoxybenzamine. No such effect could be shown with isoproterenol. The two necessary criteria for an alpha -receptor mediated response have, therefore, been fulfilled. A positive inotropic effect has been shown to be blocked specifically by alpha blocking agents, and the ability of epinephrine anti norepinephrine to produce the effect-has been shown to be greater than that of isoproterenol.
146 citations
Journal Article•
TL;DR: The times of appearance and concentrations of dopa, dopamine, norepinephrine and epinephrine were determined in the embryo and in the heart of the embryonic and developing chick and the order of appearance of each of the enzymes responsible for their synthesis was determined.
Abstract: The times of appearance and concentrations of dopa (DA), dopamine, norepinephrine and epinephrine were determined in the embryo and in the heart of the embryonic and developing chick. DA and dopamine were first detected in the heart on the 4th and 6th days of incubation, respectively. Cardiac norepinephrine and epinephrine were first detected on the 3rd day of incubation. The endogenous levels of these catecholamines and DA in the heart fluctuated throughout embryonic development and for a short time after hatching. During the remainder of development there were no further marked changes in their concentrations. In the whole embryo, DA and dopamine were first detected on the 1st and 2nd days, respectively. Norepinephrine and epinephrine were first detected on the 3rd day. As there appeared to be a somewhat orderly sequential appearance of these catechols, in the whole embryo, in accordance with the scheme for their biosynthesis, the order of appearance of each of the enzymes responsible for their synthesis was determined. Tyrosine hydroxylase, dopa decarboxylase, dopamine β-oxidase and phenylethanolamine-N-methyl transferase activities were first detected on the 1st, 2nd, 4th and 6th days of incubation, respectively.
140 citations
TL;DR: The finding that treatment with a long-acting ganglionic blocker could restore the blood pressure and the norepinephrine storage capacity in hypertensive animals to normal suggested a neurogenic component in the development of this form of hypertension.
Abstract: It has been reported that storage of norepinephrine by the sympathetic nervous system was decreased in rats made hypertensive by the administration of desoxycorticosterone trimethylacetate (DOCA) and sodium chloride. The present investigation indicated that the storage of norepinephrine was impaired at an early stage of treatment with DOCA and NaCl (1 week), and preceded the appearance of hypertension. The role of sodium and sympathetic activity, the two major factors suspected of contributing to the development of the abnormality in storage of norepinephrine, was studied in normotensive and hypertensive rats. The withdrawal of sodium from the diet of hypertensive rats for 2 weeks lowered the blood pressure to normotensive levels and simultaneously restored to normal the storage and binding capacity as well as the endogenous norepinephrine content of the sympathetic storage granules in the heart. Sodium restriction or depletion in normotensive rats caused a slight decrease in blood pressure and the retention of norepinephrine in the storage granules was increased. These findings suggested that the capacity of the sympathetic granules to bind and store norepinephrine was influenced by the state of sodium balance and showed that the capacity of storage could be correlated with the level of blood pressure. The finding that treatment with a long-acting ganglionic blocker could restore the blood pressure and the norepinephrine storage capacity in hypertensive animals to normal suggested a neurogenic component in the development of this form of hypertension.
138 citations
Journal Article•
TL;DR: Evidence that the pressor activity of PGF 2α is primarily the result of venoconstriction was obtained from experiments in which a perfusion pump was used to by-pass the right heart and a constant pressure stabilizing reservoir was placed in the venous return.
Abstract: Prostaglandin F 2α (PGF 2α ), unlike most other prostaglandins, is pressor in rats and dogs. The present investigation was undertaken to determine the mechanism of the pressor activity of this naturally occurring substance. The pressor activity in rats persisted after ganglion blockade or reserpine pretreatment, so it is neither mediated over the conventional sympathetic nervous system nor due to release of catecholamines from peripheral nerve endings. Administration of PGF 2α into the perfused limb of the dog prepared for analysis of segmental vascular pressures demonstrated that the pressor activity resulted, at least in part, from an increase in peripheral resistance, and that the increase in resistance occurred primarily in the venous segment. In unanesthetized, trained dogs prepared with electromagnetic flow-probes, PGF 2α increased both cardiac output and systemic blood pressure, leaving calculated total peripheral resistance virtually unchanged. The increase in cardiac output was not caused by a direct effect of the agent on myocardial contractility, as was demonstrated in anesthetized dogs prepared with a Walton-Brodie strain gauge arch. Further evidence that the pressor activity of PGF 2α is primarily the result of venoconstriction was obtained from experiments in which a perfusion pump was used to by-pass the right heart and a constant pressure stabilizing reservoir was placed in the venous return. In this preparation PGF 2α consistently caused an increase in reservoir volume and a marked increase in pulmonary resistance. The possible role of a substance with properties similar to those of PGF 2α in the etiology of hypertension is discussed.
125 citations
TL;DR: The absence of any effect of glucagon on glucose or lactate formation from fructose suggests that cyclic AMP does not produce any significant effect on reactions between triose-P and glucose or on the conversion of P-pyruvate to pyruVate, and gluconeogenesis appears to be as sensitive as glycogenolysis to stimulation by glucagon, catecholamines and cyclicAMP.
TL;DR: It is concluded that although ST 155 induced a certain degree of α-adrenergic blockade, this effect is not sufficient to account for the hypotensive action of the drug.
TL;DR: Results suggest that cyclic adenylic acid is an intermediate in the induction by epinephrine and that the mechanism by which it induces is different from that by which hydrocortisone operates.
Abstract: Epinephrine and the N6-O2′-dibutyryl analog of adenosine-3′,5′-cyclic phosphate both are effective inducers of tyrosine-α-ketoglutarate transaminase in explants of fetal rat liver maintained in org...
TL;DR: The data are consistent with the hypothesis of beta adrenergic blockade in bronchial asthma, and it is impossible to rule out drug effects in the group of severe asthmatic patients.
TL;DR: There seems likely that there are two separate mechanisms in the liver for controlling phosphorylase activation and glycogenolysis, and that neural control ( by sympathetic nerves) is much faster than hormonal control (by catecholamines) in rabbit liver.
TL;DR: Incubation of bovine thyroid slices in the presence of thyroid-stimulating hormone resulted in increased slice content of adenosine 3',5'-phosphate, and the response to epinephrine was antagonized well by dichloroisoproterenol, but poorly by phenoxybenzamine.
TL;DR: In man, propranolol blocked the late rise of blood lactate levels which occurs during insulin tolerance tests, indicating that muscle glycogenolysis was prevented and suggesting that propr ethanol prevents epinephrine from inducing peripheral insulin resistance.
Abstract: Since beta-adrenergic blockade dampens the rebound of plasma glucose after insulin-induced hypoglycemia in man but does not affect epinephrine-stimulated hepatic glycogenolysis, studies were undertaken to define further the metabolic role of beta-adrenergic stimulation, particularly its participation in the induction of peripheral insulin resistance by epinephrine. In in vitro studies, propranolol, a specific beta-adrenergic blocker, was shown to prevent both epinephrine and isoproterenol from inducing inhibition of insulin-stimulated glucose uptake by rat hemidiaphragm. Methoxamine, an alpha-adrenergic stimulator, did not alter insulin-stimulated glucose uptake. In man, propranolol blocked the late rise of blood lactate levels which occurs during insulin tolerance tests, indicating that muscle glycogenolysis was prevented and suggesting that propranolol prevents epinephrine from inducing peripheral insulin resistance. This might in part account for the prolonged hypoglycemia observed in propranolol-insulin tolerance tests.
TL;DR: Observations confirm and extend the findings of Paton and Zar11 that in the presence of morphine the spontaneous output of acetylcholine of the unstimulated preparation is reduced and that the evoked output per volley is low and almost constant at frequencies between 0.1 and 10/s, whereas without morphine the output each volley is usually much higher at low frequencies of stimulation and falls with increasing rates of excitation.
Abstract: MORPHINE-like drugs depress transmission across certain neuro-effector junctions1–7 ; this effect is more marked at low than at high frequencies of stimulation3,5,6 and is caused by depression of transmitter release3,5–11. Fig. 1 shows the reduction in the release of acetylcholine caused by morphine when the innervated longitudinal muscle strip of the guinea-pig ileum is stimulated transmurally. These observations confirm and extend the findings of Paton and Zar11 that in the presence of morphine the spontaneous output of acetylcholine of the unstimulated preparation is reduced and that the evoked output per volley is low and almost constant at frequencies between 0.1 and 10/s, whereas without morphine the output per volley is usually much higher at low frequencies of stimulation and falls with increasing rates of excitation.
Journal Article•
TL;DR: It was found that phentolamine and phenoxybenzamine increase the formation of radioactive norepinephrine and epinephrine in rat tissues when L-tyrosine-14C is used as a precursor but not when L
Abstract: The present study was undertaken to evaluate the effects of α-blocking agents on the rate of catecholamine synthesis in vivo . It was found that phentolamine and phenoxybenzamine increase the formation of radioactive norepinephrine and epinephrine in rat tissues when L-tyrosine-14C is used as a precursor but not when L-dopa-3H is the precursor. These findings indicate that α-blocking agents increase catecholamine synthesis by stimulating tyrosine hydroxylase activity.
TL;DR: Results suggest that respiration is coupled to phosphorylation under basal conditions in brown fat cells but that epinephrine stimulates the formation of cyclic AMP which mediates either a direct uncoupling action or an indirect one through stimulation of free fatty acid release.
TL;DR: The results support the view that adrenergic mediators participate in the neurohumoral control of GH secretion as well as other physiological constituents of hypothalamic tissue, i.e., serotonin, norepinephrine and dopamine.
Abstract: Epinephrine (0.5 μg), norepinephrine (0.5 and 0.1 μg) and dopamine (0.5 and 0.1 μg) when injected into the lateral ventricle of the rat brain, induced a depletion of growth hormone (GH) pituitary content. Unlike adrenergic compounds, other physiological constituents of hypothalamic tissue, i.e., serotonin (0.5 μg), acetylcholine (0.5 μg), vasopressin (8 mU) and oxytocin (8 mU) did not show any GHreleasing activity when given by intraventricular route. The effect of epinephrine, norepinephrine and dopamine appeared to be unrelated to changes of blood glucose or body temperature. These results support the view that adrenergic mediators participate in the neurohumoral control of GH secretion. (Endocrinology 83: 893, 1968)
TL;DR: Beta adrenergic blockade with propranolol raised the blood eosinophil count of ten normal persons by a mean of 27.8% and in individual subjects the extent of this increase was inversely proportional to the control eos inophils and directly proportional toThe reduction in resting heart rate.
Abstract: In ten normal volunteers intramuscular injection of 0.5 mg of epinephrine caused a mean drop of 61.7% in circulating eosinophils within 3-½ hours. This epinephrine-induced eosinopenia was completely blocked by oral pretreatment with 40 mg of propranolol hydrochloride. The eosinopenic action of epinephrine is apparently mediated by a beta adrenergic mechanism. Beta adrenergic blockade with propranolol raised the blood eosinophil count of ten normal persons by a mean of 27.8%. In individual subjects the extent of this increase was inversely proportional to the control eosinophil count and directly proportional to the reduction in resting heart rate. The level of circulating epinephrine may be one of the factors which normally determine the number of peripheral eosinophils. Propranolol-induced increases in the eosinophil count may serve as an index of beta adrenergic activity.
TL;DR: In patients with myocardial infarction complicated by shock, circulatory insufficiency, and transient fall in blood pressure the urinary excretion of free norepinephrine was more significantly elevated than that of epinephrine.
TL;DR: In isolated thyroid cells I-epinephrine, norepinephrine and isoproterenol consistently stimulated the accumulation and organic binding of iodine, and the effect was partially inhibited by phentolamine, but not propranolol, and hence may be mediated by alpha receptors.
Abstract: In isolated thyroid cells I-epinephrine (0.1 and 10.0 micrograms per milliliter), norepinephrine and isoproterenol consistently stimulated the accumulation and organic binding of iodine. The effect was partially inhibited by phentolamine, but not propranolol, and hence may be mediated by alpha receptors. Theophylline did not mimic or enhance the epinephrine effect, suggesting that the latter may not result from activation of adenyl cyclase.
TL;DR: Treatment of the patient's adrenal cortical insufficiency with glucocorticoids corrected his adrenal medullary response to insulin-induced hypoglycemia and may represent the first reported clinical analogue to experimental studies demonstrating that the activity of phenylethanolamine-N-methyl transferase is controlled by glucocorts.
Abstract: A 2-yr-old boy in whom hypoglycemia was associated with an ACTH deficiency (probably isolated) and with adrenal medullary unresponsiveness to insulin-induced hypoglycemia is described. This patient may represent the first reported clinical analogue to experimental studies demonstrating that the activity of phenylethanolamine-N-methyl transferase is controlled by glucocorticoids. Phenylethanolamine-N-methyl transferase is highly localized in the mammalian adrenal medulla and catalyzes the N-methylation of norepinephrine to epinephrine. Treatment of our patient's adrenal cortical insufficiency with glucocorticoids corrected his adrenal medullary response to insulin-induced hypoglycemia. The etiology of the patient's possibly isolated ACTH deficiency is unknown.
TL;DR: It is suggested that endogenous epinephrine released during stress or exercise is sufficient to suppress insulin secretion even under conditions of hyperglycemia.
Abstract: WRIGHT, PETER H., AND WILLY J. MALAISSE. Effects of epinephrine, stress, and exercise on insulin secretion by the rat. Am. J. Physiol. 214(5) : 1031-1034. 1968.-Rats were injected with guinea pig anti-insulin serum and 1251-labeled human serum albumin. After 45 min, intermittent electrical shocks were applied ; epinephrine was injected subcutaneously; or the animals swam in tepid water. All animals were killed at 75 min. Compared with endogenous insulin secreted in control animals between 45 and 75 min, significantly less secretion was observed in the three groups of treated rats. It is suggested that endogenous epinephrine released during stress or exercise is sufficient to suppress insulin secretion even under conditions of hyperglycemia.
TL;DR: The pattern of changes in blood glucose and free fatty acids after a glucose load or epinephrine injection indicated that the primary cause of hypoglycemia was enhanced glucose dissimilation by the large mass of the tumor.
Abstract: Two patients had hypoglycemia associated with large and diffuse mesenchymal abdominal tumors. In these, the pattern of changes in blood glucose and free fatty acids after a glucose load or epinephrine injection, high plasma lactate levels, low serum insulin and insulin-like activity and excessive glucose uptake by tumor tissue in vitro indicated that the primary cause of hypoglycemia was enhanced glucose dissimilation by the large mass of the tumor. Deficient compensatory glucogenesis might have been a contributing factor. Divergent patterns of the response of serum free fatty acids to epinephrine injection were related to insulin-dependent and independent hypoglycemia.
TL;DR: The effects of epinephrine and glucagon on amino acid uptake (and glucose release) by the isolated perfused rat liver were studied using a nonmetabolizable amino acid.
Abstract: The effects of epinephrine and glucagon on amino acid uptake (and glucose release) by the isolated perfused rat liver were studied using a nonmetabolizable amino acid. Pretreatment of liver donor rats with epinephrine 1 or 2 hr prior to sacrifice resulted in increased blood glucose in the intact animal and enhanced amino acid uptake by livers isolated from these animals. Epinephrine added directly to the isolated system, either as a single pulse or by constant infusion, increased the glucose in the perfusate but did not significantly alter the uptake of amino acid by the isolated liver. Glucagon, on the other hand, increased amino acid uptake by the isolated liver when the hormone was administered in vivo prior to sacrifice, or when it was added directly to the isolated system. The adrenergic blocking agent, dihydroergotamine, when administered in vivo, inhibited the effect of epinephrine on transport of amino acid into the liver. The blocking agent also reduced the effect of glucagon on amino acid transp...
TL;DR: It is concluded that epinephrine increases glucose oxidation by promoting its entry into adipose tissue and that the effect is independent of lipolysis.