Showing papers on "Epinephrine published in 1974"

Plasma Norepinephrine and Epinephrine in Untreated Diabetics, During Fasting and After Insulin Administration

Abstract: Employing a precise and sensitive double-isotope derivative technic, plasma norepinephrine and epinephrine were measured in twenty-three normal subjects and fourteen diabetics during various metabolic conditions. Patients with poorly controlled diabetes showed a rise in norepinephrine, which correlated with the degree of metabolic derangement, during resting conditions. High epinephrine values were seen only in patients with moderate to severe ketoacidosis. During exercise, diabetic patients with ketosis demonstrated large increments in plasma catecholamines as compared to normals. During insulin treatment, when good control had been achieved, plasma catecholaniine levels were similar to those in normal subjects. During prolonged fasting, plasma norepinephrine rose from 0.18 to 0.40 ng. per milliliter in four normal nonobese subjects. No change was observed in plasma epinephrine. During insulin hypoglycemia, high plasma epinephrine levels were seen only in subjects in whom the blood glucose concentration declined to values below 20 mg. per 100 ml. Plasma norepinephrine rose as blood glucose concentrations decreased even in diabetics in whom values had not reached hypoglycemic levels. No correlation was observed between plasma epinephrine and increase in pulse rate during hypoglycemia.

Pharmacological Characterization of Adrenergic Alpha and Beta Receptors Mediating the Vasomotor Responses of Cerebral Arteries Ir Vitro

Abstract: The adrenergic receptors in the isolated feline middle cerebral artery were characterized pharmacologically using a sensitive system for recording circular contractions in vitro. Epinephrine. norepinephrine, isoproterenol. and phenylephrine contracted the vessel in the mentioned order of potency. Together with the inhibitory patterns obtained with graded doses of piperoxan (reversible competitive inhibition) and dibenamine or phenoxybenzamine (irreversible competitive inhibition), these results showed that the contraction was mediated by alpha receptors. With piperoxan and norepinephrine, the mean value for pA 2 was 7.06 and for K H 1.24 x 10 -7 M. The mean value for K A calculated for norepinephrine before and after partial irreversible blockade of the alpha receptors with phenoxybenzamine was 1.73 x 10 -6 M. The norepinephrine response was not directly proportional to the amount of receptors occupied; ED 50 was reached when only about 11% of the receptors were occupied and the E Am response was obtained when 75% of the receptors were occupied. Dilation was achieved only after an active tonic contraction had been induced (with 5-hydroxytryptamine) in the vessels, and the order of potency was isoproterenol > norepinephrine - epinephrine > terbutaline. Inhibition with INPEA and propranolol was competitive, as confirmed by Arunlakshana-Schild plots, showing that the dilatory response was a beta-receptor effect. The values for pA 2 (8.78 and 9.17) and K H (2.31 x 10 -9 M and 1.77 x 10 -9 M) for propranolol were indistinguishable in tests with terbutaline and isoproterenol, respectively. Comparison of the relative potencies of norepinephrine and epinephrine as well as isoproterenol and terbutaline suggested that the receptors were of the beta 1 type.

Glucagon Secretion from the Perfused Rat Pancreas STUDIES WITH GLUCOSE AND CATECHOLAMINES

Abstract: The isolated in situ perfused rat pancreas was used to study glucose and catecholamine control of glucagon secretion, and to investigate the possible role of endogenous cyclic AMP as a mediator of this secretory process. When perfusate glucose was acutely dropped from 100 to 25 mg/100 ml, glucagon was released in a biphasic pattern with an early spike and a later plateau-like response. 300 mg/100 ml glucose suppressed glucagon secretion to near the detection limit of the radioimmunoassay (15 pg/ml). When perfusate glucose was dropped from 300 to 25 mg/100 ml, a delayed, relatively small peak occurred suggesting persisting alpha cell suppression by prior high glucose exposure. 2-Deoxy d-glucose stimulated glucagon secretion and inhibited insulin secretion. Glucagon was secreted in a biphasic pattern in response to both 2.7 × 10-7 M epinephrine and norepinephrine. The glucagon response to epinephrine was markedly suppressed by glucose at 300 mg/100 ml, and the biphasic response pattern was obliterated. Glucose evoked a two-phase insulin secretory pattern, and the second phase was markedly and rapidly inhibited by epinephrine. Pancreases were perfused with glucose at 300 mg/100 ml which was then lowered to 80 mg/100 ml. 5 min later, epinephrine was infused and definite blunting of the first-phase spike occurred. 10 mM theophylline produced modest rapid uniphasic stimulation of glucagon release, and, in addition, caused enhancement of epinephrine-stimulated glucagon release. An inhibitory influence upon epinephrine-stimulated glucagon was observed as well. Insulin secretion was stimulated by 10 mM theophylline, and this stimulation was inhibited by epinephrine.

Plasma Catecholamines and Carbohydrate Metabolism in Patients with Acute Myocardial Infarction

Abstract: Blood glucose, glucose tolerance, serum insulin, free fatty acids in serum, plasma noradrenaline, and plasma adrenaline were measured in 10 patients with acute myocardial infarction (AMI) as well as in healthy subjects. Both noradrenaline and adrenaline in plasma were elevated in patients with AMI, the level being fairly constant in the individual patients and dependent on their degree of illness. In the fasting state, blood glucose, serum insulin, and free fatty acids were elevated in patients with AMI. Plasma noradrenaline showed a highly significant correlation with the fasting blood glucose concentration, but not with serum insulin or free fatty acids. The concentration of free fatty acids in serum could be predicted only if both plasma noradrenaline and the basal insulin concentration were known. Intravenous glucose tolerance was reduced in patients with AMI, especially in patients with high plasma noradrenaline and a low initial rise in insulin. There was a significant negative correlation between the initial rise in insulin expressed in percentage of the basal insulin concentration and the plasma noradrenaline level. The statistical effects of serum insulin and plasma noradrenaline on the glucose tolerance could not be separated from each other. The decline in free fatty acids after intravenous injection of glucose showed a negative correlation with plasma noradrenaline and a positive correlation with the initial rise in insulin. Plasma adrenaline did not correlate with any of the metabolic parameters mentioned above. The plasma noradrenaline concentration was elevated to such a degree in patients with AMI that the observed changes in metabolism might have been caused directly by the circulating noradrenaline. During the glucose tolerance tests, the effects of noradrenaline was probably carried out indirectly via a suppression of insulin secretion. It is conceivable that any effect of plasma noradrenaline on the basal insulin secretion was neutralized by the fasting hyperglycemia.

Release of renal prostaglandin by catecholamines: relationship to renal endocrine function

Abstract: Epinephrine and norepinephrine caused vasoconstriction and prostaglandin (PG) release when administered to the isolated perfused rabbit kidney. Dopamine was only about 0.1% as potent as epinephrine as a PG releaser, and isoproterenol did not cause renal PG release. Catecholamine-induced PG release thus appears to be mediated by alpha adrenergic receptor site stimulation, and this was confirmed by the finding that blockade was achieved with phenoxybenzamine but not propranolol. Phenoxybenzarnine did not block PG release induced by angiotensin II, but indomethacin (PG synthesis inhibitor) blocked all PG release. Renal nerve stimulation caused the rabbit kidney to release PG, and this release was blocked by phenoxybenzamine or indomethacin. Paradoxically, tyramine did not cause PG release. Renal ischemia caused PG release which was blocked by indomethacin but was not blocked by phenoxybenzamine and/or propranolol.

Neurogenic and Humoral Factors Controlling Vascular Resistance in the Spontaneously Hypertensive Rat

Abstract: The mechanism of sustained hypertension in spontaneously hypertensive rats has not been elucidated. In the present investigation, vasoconstrictor responses to a variety of neurogenic and humoral interventions were studied in the perfused hindquarters of Okamoto spontaneously hypertensive rats and normotensive Wistar rats. In addition, central sympathetic electrical discharge was measured. Vasoconstrictor responses in the hindquarters to lumbar sympathetic nerve stimulation were unchanged or reduced in the spontaneously hypertensive rats, but the responses to intra-arterially administered norepinephrine and epinephrine were enhanced. Vascular responses to intra-arterially administered tyramine, angiotensin, and barium chloride were also greater in the spontaneously hypertensive rats. Vascular resistance was significantly higher in the spontaneously hypertensive rats, and this difference remained following bilateral lumbar sympathectomy. Despite elevated systemic blood pressure, integrated nerve activity at rest was not different in the spontaneously hypertensive rats. The inverse relationship between arterial blood pressure and sympathetic nerve discharge was not different between spontaneously hypertensive and control rats when pressure was either raised or lowered. Changes in efferent sympathetic discharge produced by activation of chemoreceptors (asphyxia) were somewhat less in the spontaneously hypertensive rats. The contribution of low-pressure baroreceptors (45° tilt) to activation of sympathetic vasomotor tone was not different in the spontaneously hypertensive rats despite a greater decline in systemic blood pressure during the procedure. These data demonstrate that established hypertension in the spontaneously hypertensive rat does not derive from either enhanced central adrenergic discharge or altered central integration of afferent information from peripheral sensory receptors but may result from humoral (e.g., increased reactivity to vasoconstrictors) or structural factors.

Adenyl Cyclase in Normal and Pathologic Human Muscle

Abstract: Adenyl cyclase activity in normal human muscle is stimulated four to seven times by epinephrine and about 18 times by sodium fluoride. The enzyme is present in all particulate fractions of muscle (myofibrils, mitochondria, sarcoplasmic reticulum) but not in the soluble phase. The highest specific activity is found in isolated plasma membrane. Basal enzyme activity was normal in muscle from patients with Duchenne or facioscapulohumeral dystrophy but the response to epinephrine was about 30% of normal and the response to sodium fluoride about half normal. In polymyositis, responses were normal, and intermediate values were found in myotonic dystrophy. In denervated muscle, responses were enhanced. In fetal muscle there was no response to epinephrine but sodium fluoride stimulated, suggesting that the mechanisms of these agents differ.

Response of leucocyte adenyl cyclase to isoprenaline and effect of alpha-blocking drugs in extrinsic bronchial asthma.

Abstract: The finding by several workers that biochemical responses to catecholamines are diminished in asthmatic patients during periods of active asthma as compared to normal subjects has led to the recognition of the beta-adrenergic blockade phenomenon, a common accompaniment of extrinsic bronchial asthma. Using an intact cell method to measure leucocyte adenyl cyclase activity, we have been able to show that there is a noticeably reduced responsiveness of this enzyme system (which is now identified with beta-receptor function) to isoprenaline in the leucocytes of patients suffering from acute bronchial asthma, but that asthmatic patients in remission could not be distinguished from normal persons in this respect. Evidently the defective beta-receptor function may be associated with overactivity of the alpha-receptors in acute bronchial asthma, since the responsiveness to isoprenaline stimulation could be restored towards normal by concomitant treatment of the leucocytes of these patients with alpha-receptor blocking drugs such as phentolamine or thymoxamine. Ouabain, though somewhat less potent, also enhanced responsiveness to isoprenaline stimulation. The relation of these results to the clinical observation of adrenaline resistance in active asthma suggests that alpha-receptor blocking drugs may be of value in restoring the sensitivity of beta-receptors to sympathomimetic amines.

Effects of β adrenergic blockade on plasma catecholamines in exercise

Abstract: IT is well established that physical exercise causes an increase in sympathetic activity, as shown by rises in the levels of plasma and urine catecholamines1. This increase in endogenous adrenergic activity can be used to study the effects of sympathetic stimulation. Such studies usually compare a control situation with one in which either α or β adrenergic receptor activity is blocked pharmacologically, thereby allowing study of both the blocked and unblocked receptors. Beta blocking drugs have been used in this way to study changes in carbohydrate metabolism2, free fatty acid metabolism3, and blood coagulation and fibrinolysis4 induced by exercise.

In vivo changes of cerebral cyclic adenosine 3',5'-monophosphate induced by biogenic amines: association with phosphorylase activation.

Abstract: —The intravenous injection of adrenaline, isoprenaline and histamine to 4-6-day-old chicks resulted in a rapid increase in the cyclic AMP content of cerebral hemispheres that had been removed and frozen within 0·5 s using a freeze-blowing technique. Noradrenaline, dopamine, adenosine, 5-HT and acetylcholine did not significantly alter the nucleotide concentration in vivo. Addition of adrenaline, isoprenaline and histamine to incubated chick cerebral cortex slices also increased the cyclic AMP content of the tissue. Noradrenaline was considerably less potent than these amines and adenosine was ineffective. Low phosphorylase a levels (16 per cent of total activity) were observed in instantaneously frozen cerebral hemispheres of untreated chicks. The injection of adrenaline, isoprenaline and histamine resulted in a rapid conversion of phosphorylase b to a and a significant fall in tissue glycogen. Administration of noradrenaline was without effect on the relative forms of phosphorylase and also failed to influence cerebral glycogen. Phosphorylase activation was not observed in chick cerebral slices under conditions producing large increases in cyclic AMP. It is suggested that in vivo phosphorylase activation and subsequent glycogenolysis may occur, at least in part, in glia and that these cells may be damaged during preparation of cerebral slices. The results provide evidence of a metabolic role for cyclic AMP in cerebral tissue.

Tryptaminergic and dopaminergic responses of schistosoma mansoni

Abstract: Pharmacological evidence is reported indicating that 5-hydroxytryptamine is an excitatory neurotransmitter in Schistosoma manasoni . The stimulation of the motor activity of adult schistosomes brought about by cholinergic blockade is abolished 1) by bromlysergic acid diethylamide and other 5-hydroxytryptamine antagonists and 2) by prior 5-hydroxytryptamine depletion brought about by exposure of the parasites to chlorimipramine and reserpine. Whereas catecholamines have no effect on the motor activity of schistosomes, low concentrations of dopamine, norepinephrine and epinephrine (but not isoproterenol) produce a lengthening response of the worm which is ascribed to a relaxation of the longitudinal musculature. The same response was induced by apomorphine, considered to be a specific dopamine receptor agonist, but not by clonidine, a specific norepinephrine receptor agonist. Apomorphine and dopamine were more potent in this respect than norepinephrine and epinephrine. These effects are blocked more effectively by dopamine-blocking agents than by alpha and beta adrenergic blockers. Male worms from single-sex infections differed in their lengthening response from males paired with females.

Response of ovine uterine blood flow to epinephrine and norepinephrine.

Abstract: SummaryThe effect of the infusion of epinephrine and norepinephrine directly into the lumen of either uterine artery was studied in unanesthetized, unstressed sheep in both the nonpregnant and pregnant state. The vasoconstrictive response to those catecholamines was found to lie within a narrow range; a 50% reduction of flow was caused by a 3-13 ng/ml arterial blood concentration of epinephrine and 2-10 ng/ml of arterial blood concentration of norepinephrine. This method of in vivo uterine artery infusion plus uterine blood flow measurement appears well-suited for precise quantitative analysis of the reaction of the uterine vascular bed to pharmacologic agents.

A role for nicotinic receptors in the regulation of the adenylate cyclase of adrenal medulla

Abstract: The activities of phosphodiesterase and adenylate cyclase and the concentration of catecholamines, 39,59-cyclic adenosine monophosphate (cAMP) and protein in the capsule, cortex and medulla of normal and denervated adrenals were measured. Denervation reduces the concentrations of catecholamines and the activity of adenylate cyclase in medulla. All the other parameters are unchanged by denervation. Exposure to 4°C causes the accumulation of cAMP in cortex and medulla; denervation reduces cAMP accumulation in medulla but not in cortex. Carbamylcholine (1.3 µmol/kg i.p.) increases the cAMP concentrations in adrenal cortex and medulla of intact and denervated adrenal. Maximal effects are elicited by 5.4 µmol/kg i.p. Bethanechol is less active than carbamylcholine in increasing cAMP concentrations of adrenal tissues. Mecamylamine (15 µmol/kg i.p.) and hexamethonium (45 µmol/kg i.p.) fail to change cAMP concentrations in adrenal parts but block the increase of cAMP elicited by either cold exposure or by carbamylcholine injections. Hexamethonium blocks the increase of cAMP elicited by cold exposure in cortex of denervated adrenal. Injections of epinephrine, tyramine, isoproterenol and amphetamine in doses that increase the concentrations of cAMP in other tissues fail to increase cAMP concentrations in adrenal medulla. In vitro , none of the drugs mentioned inhibit phosphodiesterase activity; adrenocorticotropin stimulates adenylate cyclase activity of adrenal cortex homogenates but not that of homogenates of adrenal medulla. Carbamylcholine (0.5 mM) increases the rate of cAMP accumulation in slices of adrenal medulla but fails to change that of cortical slices. In contrast, adrenocorticotropin stimulates cAMP accumulation in slices of adrenal cortex but not in slices of adrenal medulla.

Effects of adrenergic agonists and antagonists on potassium metabolism.

Abstract: Epinephrine and isoproterenol were previously found to protect animals against an infusion of KCl which was lethal in most animals. The protection was correlated with a hypokalemic action of the amines ( i.e. , an ability to attenuate the hyperkalemia induced by the KCl infusion). In the present study on cats, salbutamol and soterenol were found to exert a similar action. Norepinephrine (1 µg/kg/min) was considerably less effective than an equal dose rate of epinephrine; the former produced some reduction of the hyperkalemia but did not significantly decrease the mortality produced by KCl infusion. The beta -1 stimulant, 1-isopropylamino-3-(2-thiazoloxy)-2-propanol, had no effect on the hyperkalemia or mortality produced by KCl infusion. The hypokalemic action of epinephrine was correlated with significantly higher levels of K + in cardiac and skeletal muscle. An infusion of glucose, which produced blood glucose levels higher than in the epinephrine series, did not have a hypokalemic or protective effect against KCl infusion. The hypokalemic and protective effects of epinephrine were not modified by acute pancreatectomy. Pretreatment with nonselective beta blocking agents (propranolol and sotalol) and with beta -2 blocking agents (butoxamine and H35/25) reduced or abolished the hypokalemic and protective actions of epinephrine in cats given KCl. The alpha blocking agent, phenoxybenzamine, and the beta -1 antagonist, practolol, did not significantly reduce these actions of epinephrine. The results indicate that beta -2 receptors subserve a hypokalemic action which is responsible for the protective effect of sympathomimetic amines against potassium intoxication. This hypokalemic action appears related to increased entry of K + into cells.

Interaction of glucocorticoids and bronchodilators on isolated guinea pig tracheal and human bronchial smooth muscle.

Abstract: Recent investigations indicate that glucocorticoids are capable of enhancing the responses to catecholamines on vascular smooth muscle The present study was undertaken to compare the interaction of three glucocorticoids (hydrocortisone sodium succinate, methyl prednisolone sodium succinate, and dexamethasone phosphate) with a series of catecholamine and noncatecholamine beta sympathomimetic bronchodilators on guinea pig tracheal and human bronchial smooth muscle Log dose-response lines were obtained for isoproterenol (ISO), epinephrine (EPI), norepinephrine (NOR), salbutamol (SAL), and metaproterenol (META) in the absence and presence of varying concentrations of three different glucocorticoids Hydrocortisone and methyl prednisolone potentiated the responses to all beta agonists on the guinea pig trachea The degree of potentiation was greatest with ISO, significantly less with EPI, and much less with NOR, SAL, and META Dexamethasone, however, produced only minimal alterations of the responses to the

Acute hormonal regulation of cyclic AMP content and glycogen phosphorylase activity in fetal liver in organ culture.

Abstract: Acute hormonal regulation of fetal rat liver cyclic AMP content and glycogen phosphorylase activity was examined in an organ culture system using explants from term fetuses. Phosphorylase was rapidly activated by epinephrine and glucagon; the respective minimally effective concentrations were 2 X 10−7M and 10−8M. The characteristics of the adrenergic response were denned. Following the addition of a high concentration (10−5M) of epinephrine: Phosphorylase activity increased to a maximum at one minute (the earliest time point examined) and remained unchanged for at least 30 min; cyclic AMP levels were also maximally elevated by one minute but then declined over the next 30 min. The beta antagonist propranolol blocked both effects of epinephrine; the alpha antagonist phentolamine was without effect. The predominantly beta agonist isoproterenol was much more effective in elevating cyclic AMP levels and in activating phosphorylase than the predominantly alpha agonist phenylephrine. We conclude: i. fetal rat l...

Responses of adipose tissue to sequential lipolytic stimuli.

Abstract: Following stimulation of rat epididymal adipose tissue segments with epinephrine, cyclic AMP levels increase to maximum values by 5 min; thereafter, cyclic AMP levels decline, reaching values which may not be significantly different from prestimulation levels. When additional epinephrine was added to the incubation medium or when stimulated tissues were transferredto fresh epinephrine containing media, the anticipated second increase in cyclic AMP was absentor greatly diminished. Addition ot theophylline to the restimulation medium failed to overcome the apparent “refractoriness” to the second epinephrine stimulation. The apparent“refractoriness” to epinephrine stimulation was also induced by prior exposure toACTH but not to theophylline, suggesting that lipolysis per se is not the cause of unresponsiveness. Becausetissues remain unresponsive even when transferred to fresh medium, the “refractoriness” cannot be ascribed to the release of an inhibitory substance into the medium. All epinephrine and theophy...

The effects of epinephrine, prostaglandins, and their antagonists on adenosine cyclic 3',5'-monophosphate concentrations and motility of the rat uterus.

Abstract: Interactions of substances which induce contractions (prostaglandins, oxytocin) and of epinephrine, which induces relaxation, with the adenylate cyclase system were examined in estrogen-treated rat myometrium. Epinephrine and prostaglandin E1 (PGE1) (also PGE2) stimulated adenylate cyclase activity. The response to both agents was very rapid, being detectable at 30 sec. Propranolol inhibited the activation of adenylate cyclase by epinephrine but not that by PGE1. A single adenylate cyclase appeared to be involved in stimulation by both agonists. PGF1α, PGF2α, and oxytocin had no significant effect on adenosine cyclic 3',5'-monophosphate (cAMP) concentrations. All the E and F prostaglandins analysed elicited contractions in rat uteri; therefore PGE1 stimulated contractions although elevating cAMP levels. Epinephrine antagonized contractions evoked by PFG2α and oxytocin as well as by PGE1. The relaxing effect of epinephrine could be mimicked by dibutyryl-cAMP and inhibited by propranolol. There seemed to be a good correlation between the stimulation of adenylate cyclase by epinephrine and its effect on motility, implicating a role for cAMP in smooth muscle relaxation. Such a correlation could not be demonstrated for PGE1. Two prostaglandin antagonists, polyphloretin phosphate and 7-oxa-13-prostynoic acid, blocked the prostaglandin E- and F-induced contractions but did not alter the ability of PGE1 to raise cAMP levels. The results suggest that interaction with adenylate cyclase is not a prerequisite for the prostaglandins to induce contractions in uterine smooth muscle. The differences in the action of epinephrine and PGE on uterine motility may reflect compartmentalization of the cAMP formed in response to these agents. ACKNOWLEDGMENTS We are grateful to Professor H. Clauser for advice and helpful discussions throughout this work. We would like to thank Dr. J. E. Pike, Upjohn Company, Kalamazoo, who provided us with the prostaglandins; Dr. J. Fried, for the generous gift of 7-oxa-13-prostynoic acid; and Dr. B. Vargaftig, for the polyphloretin phosphate (provided to him by Dr. B. Hogberg). Finally, we express our thanks to Dr. G. Vassort and Mrs. M. F. Sire for the histological preparations; to Mrs. Robichon, for technical assistance, and to Mrs. Crosnier, for typing the manuscript.

Effects of ketone body infusion on hypoglycemic reaction in postabsorptive dogs

Abstract: The hypoglycemic reaction following the injection of a large dose of insulin was studied in postabsorptive, anesthetized dogs. The rate of epinephrine release into the adrenal vein was monitored to provide an index of hypoglycemic stress at the level of the central nervous system. As expected an acute discharge of epinephrine was observed during the insulin-provoked hypoglycemia. It is shown that this epinephrine discharge can be prevented by infusing ketone bodies to sustain blood ketone body concentrations in the range of 1 to 2 mM. Arterial-venous differences across the head during hypoglycemia were of 0.20 ± 0.03 mmoles/liter for the extraction of ketone bodies. Since basal arterial-venous difference due to glucose oxidation were of 0.24 ± 0.11 mmoles/liter, it is concluded that the brain of the dog has the ability to use quantitatively important amounts of ketone bodies without prior adaptation to starvation.

Catecholamine-induced lipolysis in swine

Abstract: 1. 1. Catecholamines stimulate lipolysis in in vitro preparations from swine. The order of effectiveness of the adrenergic agonists was isoproterenol > norepinephrine > epinephrine, and the relative potency was ca. 1 : 15 : 35. 2. 2. The use of adrenergic blocking agents indicated that the epinephrine agonistic response was inhibited by low concentrations of propanolol and alprenolol and by higher concentrations of sotalol. 3. 3. The inhibition by these β-adrenergic antagonists plus the greater response to isoproterenol indicates that the receptors were primarily of the β-type. 4. 4. The epinephrine agonistic response could be blocked by phentolamine, an α-adrenergic blocker but only at extremely great concentrations.

Interaction between Adrenergic and Cholinergic Systems: Presynaptic Inhibitory Effect of Noradrenaline on Acetylcholine Release

Abstract: Noradrenaline and adrenaline inhibit acetylcholine release due to nerve activity, through α-adrenoceptors. The inhibition of acetylcholine release by the adrenergic transmitters is, in fact, a rather economical way for the adrenergic (orthosympathetic) nervous system to counteract the parasympathetic nervous system. It is shown that there is a permanent adrenergic control of acetylcholine output. The increase in acetylcholine output after catecholamine depletion or α-blockade of nervous tissue only represents partial removal of an adrenergic restraint. The modulatory role of catecholamines on acetylcholine release mechanism seems to be of physiological importance. Furthermore, it is also shown that acetylcholine may regulate its own release by a negative feedback mechanism. Although this mechanism operates in brain cortex, no such phenomenon, however, was found in the Auerbach plexus.