Adrenergic activity of the avian oviduct in vivo

The effect of noradrenaline or isoproterenol, alone or in the presence of an alpha (phenoxybenzamine) or beta (propranolol) adrenergic blocking drugs on the oviducts of anesthetized laying hens was investigated. The results show that both alpha and beta adrenergic activity is present in the avian oviduct with the exception of the uterus which does not appear to have alpha excitatory activity. Norepinephrine induced a strong contraction followed by a brief relaxation period in the infundibulum, magnum and is thmus; administration of phenoxybenzamine blocked this response in all the three segments, indicating the presence of alpha adrenergic receptors. The uterus, however, exhibited an inhibitory response in the majority of the hens and this response was not affected by the administration of phenoxybenzamine. Isoproterenol always induced relaxation in all the four segments of the oviduct. This response was blocked by propranolol, a beta adrenergic blocker, indicating the presence of beta adrenergic receptors. The role of autonomic nerves innervating the reproductive tract in the regulation of reproduction is discussed.     

The effect of alpha and beta adrenergic receptor stimulation on the adenylate cyclase activity of human adipocytes.

The effects of the mixed agonist epinephrine and the beta agonist isoproterenol, each alone and in combination with the alpha adrenergic blocker phentolamine and the beta blocker propranolol on the adenylate cyclase activity of human adipocyte membrane fragments were determined in a calcium free buffer. Neither phentolamine (10 muM) nor propranolol (32 muM) affected basal adenylate cyclase activity. Epinephrine (10 muM) stimulated adenylate cyclase activity and this effect was slightly enhanced by phentolamine. The combination of epinephrine plus propranolol depressed adenylate cyclase below the basal level. Isoproterenol (10 muM) markedly stimulated adenylate cyclase; the addition of phentolamine caused an equivocal further increase while the addition of propranolol depressed adenylate cyclase activity to, but not below, the basal level. These findings are consistent with the hypothesis that human adipocytes have both alpha and beta adrenergic receptors and that these receptors are associated with the cell membrane adenylate cyclase system.     

Effects of epinephrine on glucose-1,6-bisphosphate and carbohydrate metabolism in skin

1. Injection of epinephrine induced in skin a decrease in the level of glucose-1,6-bisphosphate (Glc-1,6-P2), which was accompanied by correlated changes in the activities of several enzymes which are modulated by this regulator. 2. These effects were blocked by the alpha adrenergic blocker phentolamine, in contrast to muscle where the hormone increases Glc-1,6-P2, acting through beta receptors. 3. The changes in the enzymes' activities, as well as in glycogen and lactate content induced by epinephrine, reveal that the hormone causes, in skin, a stimulation of glycogenolysis and glycolysis, as well as an acceleration of pentose phosphate pathway. 4. The reduction in glycogen content induced by epinephrine, was blocked by the beta adrenergic blocker propranolol, whereas the hormone's effects on the other processes were mainly mediated through alpha receptors.     

Alpha and beta adrenergic control of contraction force of perch heart (Perca fluviatilis) in vitro

Noradrenaline showed a negative inotropic effect on the isolated electrically triggered atrium of the perch. The effect was stronger at lower temperature and was antagonized by an alpha adrenergic blocker, phentolamine. The inotropic effect of adrenaline was dependent on incubation temperature. The effect was negative at 15 C but biphasic at 24 C, where with increasing adrenaline concentration a positive inotropic effect was followed by negative inotropy. Phentolamine not only antagonized the negative inotropic effect of adrenaline at 15 degrees C but changed it to positive. This positive inotropic effect was antagonized by a beta adrenergic blocker, propranolol. On the triggered ventricular strip adrenaline had no effect at 6 or 15 C, but increased contraction force at 24 C. It can be suggested that in the perch heart atrium there is an activity balance of alpha and beta receptors, which mediate the negative and positive inotropic control, respectively. As in higher vertebrates, alpha adrenergic activation decreases and beta activation increases by agonists in the following order: noradrenaline, adrenaline and isoprenaline. The balance changes towards increased beta activity when temperature rises.     

Histofluorescent labelling of catecholaminergic structures in rotifers (Aschelminthes) in whole animals

1. Catecholaminergic neuronal structures were investigated in the rotifers Brachionus plicatilis, Asplanchna priodonta and Asplanchna herricki, using three different aqueous histofluorescent methods. 2. The adrenergic receptors were labelled using the dansyl analog of propranolol, a beta-adrenergic blocker. Catecholamine neurotransmitters were visualized by derivatizing with glyoxylic acid and formaldehyde respectively. 3. Although all three methods lead to similar results, dansyl-propranolol gave the most rapid and strong fluorescence. 4. The results reveal a complex and highly developed catecholaminergic neuronal system in all adult organs and sensory structures. While developed embryos in the egg show strong fluorescence, immature eggs do not.     

Rotifer neuropharmacology--II. Synergistic effect of acetylcholine on local anesthetic activity in Brachionus calyciflorus (Rotifera, Aschelminthes)

A number of compounds showing general anesthetic action in the rotifer Brachionus calyciflorus were investigated in the presence of acetylcholine. Non-ionizing anesthetics, including tricaine, showed no interaction with acetylcholine. However, highly ionized compounds like the local anesthetics procaine and lidocaine, the muscarinic blocker and local anesthetic atropine, and the beta-adrenergic blocker propranolol showed a synergistic effect with acetylcholine. ACh increased the general anesthetic effect of these compounds in a statistically highly significant dose-dependent fashion. To account for the mechanism of this unusual and novel effect it is proposed that these compounds interact with the anesthetic binding site of the rotifer cholinoceptor ionophore in the open state. It is also proposed that non-ionizing compounds have a general membrane effect only. In addition to anesthesia, atropine and propranolol cause foot paralysis in B. calyciflorus. This other novel effect is also enhanced by acetylcholine as well as decamethonium, a neuromuscular blocker.     

Role of catecholamines in the inhibitory effect of immobilization stress on testosterone secretion in rats

Immobilization stress applied for 6 h induced, in adult male rats, a rise of epinephrine (E) and norepinephrine (NE) plasma levels and a decrease of baseline plasma testosterone (T) values and of human chorionic gonadotropin (hCG)-induced T response. Treatment of the animals for 5 weeks with guanethidine (G), a sympathetic neuron toxic agent, significantly decreased E and NE responses to stress and partly antagonized the inhibitory effects exerted by immobilization on T biosynthesis. Adrenalectomy totally suppressed circulating E and reduced the stress-induced NE increase while partly antagonizing the inhibitory effects exerted on T biosynthesis. Combined G and adrenalectomy treatments totally suppressed plasma E and NE, and completely blocked the effects of immobilization on T levels. Treatment of the animals with the alpha 1-adrenergic blocker, prazosin, and the beta 1-adrenergic blocker, metoprolol, did not modify the effects of stress on T biosynthesis. Treatment with propranolol or with butoxamine, a nonspecific beta- and a specific beta 2-adrenergic receptor blocker, respectively, antagonized the testicular hyposensitivity to hCG induced by stress. Stress- or treatment-induced changes of plasma luteinizing hormone (LH) and hCG levels were not consistently correlated with plasma T modifications. These findings suggest that at least part of the inhibitory effects of immobilization stress on T biosynthesis is exerted by catecholamines through a beta 2-adrenergic receptor.     

Neuropharmacology of rotifer feeding,oviposition, and anesthesia

Effect of acetylcholine and anticholinergic drugs on feeding, oviposition, and anesthesia in rotifers was investigated. Neurotransmitter as well as antagonist drugs inhibited feeding in Brachionus calyciflorus in a dose-dependent manner. Most antagonist drugs caused an oscillating tachyphylaxis (drug habituation): the drug effect wore off and returned several times within an hour. Acetylcholine inhibited oviposition in Philodina acuticornis, and this effect was antagonized by all groups of anticholinergic drugs. The strongest antagonism was caused by neuromuscular blockers, and thus the cause of oviposition inhibition may be a cloacal sphincter spasm. Acetylcholinesterase inhibitory insecticides also antagonize the acetylcholine effect. Acetylcholine potentiates the anesthetic activity of ionizing local anesthetics (procaine, lidocaine) as well as that of atropine and the beta-adrenergic blocker propranolol. Muscarinic antagonists (atropine, benactyzine) and propranolol caused foot paralysis in B. calyciflorus, which is also potentiated by acetycholine. Further details of these results are given by Nogrady and Keshmirian (1986a, b).     

Effect of glucagon and some other alpha and beta adrenergic agonists and antagonists on alanine amino transferase of perfused rat liver

Summary Glucagon increased alanine amino transferase (AAT) activity in perfused rat liver by about 90% over control. Propranolol, the beta receptor antagonist, abolished the effect of glucagon on this enzyme. Well known beta receptor agonists like isoproterenol, norepinephrine and epinephrine also increased the enzyme activity under identical condition and the enhancement was similarly abolished by propranolol. These experiments suggest that the effect of glucagon on AAT was mediated through beta adrenergic receptor. However, the interesting observation was that phenylephrine, alpha receptor agonist and phenoxybenzamine and tolazoline, two alpha receptor antagonists, increased the AAT activity like glucagon in perfusion experiments and the effects of all these three agents were also abolished by propranolol. Glucagon, when perfused with phenoxybenzamine showed some additive effect. From all these results we are proposing that in our system phenoxybenzamine is acting as beta agonist although it is known to be an alpha antagonist.     

Effect of adrenergic and cholinergic antagonists on post-hemorrhagic erythropoiesis in rats

Experiments were carried out in albino rats to find out the effect of propranolol, priscol and atropine on post-hemorrhagic erythropoiesis. Administration of either propranolol or priscol decreased reticulocyte response following hemorrhage, whereas administration of atropine produced no change. The results indicate that alpha as well as beta adrenergic systems participate in the control of erythropoiesis following hemorrhage, whereas parasympathetic system does not take part.     

Comparative regulation of potassium and amphetamine induced release of 3H-norepinephrine from rat brain via presynaptic mechanisms.

This study examined the ability of various drugs to modify the potassium (K) or d-amphetamine (d-A) induced release of ³H-norepinephrine ³HNE) from chopped rat cortical tissue. The K induced release of the transmitter, which occurs from reserpine sensitive sites of cortical tissue, was significantly reduced by the beta receptor antagonist propranolol, the alpha receptor agonist clonidine and also by PGE₂. Pretreatment with eicosatetrynoic acid, an inhibitor of prostaglandin synthesis, did not influence the effect of clonidine on ³HNE release; thus this latter effect appears to be independent of enhanced prostaglandin formation. The proposed alpha receptor mediated negative feedback exhibits stereospecificity since addition of exogenous 1-, but not d-, NE decreased release of the transmitter. Blockade of alpha receptors by phentolamine or stimulation of beta receptors by isoproterenol significantly enhanced the K induced release of ³HNE from cortical tissue. By contrast, the d-A induced release of ³HNE which occurs from reserpine-insensitive sites, was reduced by propranolol and clonidine; and was not altered by phentolamine, isoproterenol or PGE₂. These data indicate that the K, but no d-A, induced release of ³HNE from cortical tissue is modified in accordance with postulated presynaptic negative and positive feedback mechanisms.     

Prejunctional beta 1-adrenoceptors inhibit cholinergic transmission in canine bronchi

The aim of the present study was to determine in canine bronchi the effects produced by norepinephrine (released from adrenergic nerve terminals) on cholinergic neurotransmission. Electrical stimulation of canine bronchi activates cholinergic and adrenergic nerve fibers. The adrenergic neuronal blocker, bretylium tosylate, inhibited the increase in [3H]norepinephrine overflow evoked by electrical stimulation but did not prevent that caused by the indirect sympathomimetic tyramine. During blockade of the exocytotic release of norepinephrine with bretylium, the pharmacological displacement of the sympathetic neurotransmitter by tyramine significantly decreased the contractions evoked by electrical stimulation but did not affect contractions caused by exogenous acetylcholine. Metoprolol, a beta 1-adrenergic antagonist, abolished and propranolol significantly reduced the effect of tyramine during electrical stimulation. alpha 2-Adrenergic blockade, beta 2-adrenergic blockade, or removal of the epithelium did not significantly affect the response to tyramine. These results suggest that norepinephrine when released from sympathetic nerve endings can activate prejunctional inhibitory beta 1-adrenoceptors to depress cholinergic neurotransmission in the bronchial wall.     

Ionic requirements for catecholamine aggregating actions on the teleost Poecilia reticulata melanophores.

Norepinephrine (NE) and phenylephrine (Phe) were employed to study the ionic requirements for alpha adrenoceptor activation in the teleost Poecilia reticulata melanophores. As expected the beta adrenoceptor blocker, propranolol, increased the sensitivity of the preparation to NE (5.8 times), and was therefore employed in all the experimental procedures. Neither cocaine (a neuronal uptake blocker) nor dexamethasone (an extraneuronal uptake blocker) enhanced the sensitivity of the preparation to NE, suggesting that these inactivating mechanisms would not play a role in P. reticulata pigmentary system. However, in the absence of calcium, the dose-response curve (DRC) to NE was displaced to the left about 3.5 times, whereas the DRC to Phe was not affected. These results indicate that a neuronal uptake is active, but was not demonstrated by the classical pharmacological tools, probably due to an assymmetric display of the nervous endings. The DRC to NE was rightward displaced (14.1 times) in the presence of the calcium channel blocker Verapamil, whereas the DRC to Phe was not affected. These data suggest that P. reticulata melanophores possess a mixed population of alpha 1 and alpha 2 adrenoceptors, the activation of the latter eliciting an extracellular calcium influx. In sodium-free saline, the DRC to NE was rightward shifted (6.6 times) and the response to Phe was impaired in such a way that the maximal response was not achieved. The DRC to both NE and Phe were rightward displaced (7.9 and 2.7 times respectively) in the presence of the sodium channel blocker tetrodotoxin (TTX) 10(-7)M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium dependent aggregation of marine sponge cells is provoked by leukotriene B4 and inhibited by inhibitors of arachidonic acid oxidation

The mechanism of agonist-induced desensitization of the beta adrenergic receptor coupled adenylate cyclase has been studied in a smooth muscle cell line, BC3H-1, which expresses both alpha and beta adrenergic receptors and nicotinic receptors. beta receptors have been investigated in intact cells using as radioligand 3HCGP-12177, an hydrophilic compound which labels only surface receptors. The treatment of BC3H-1 cells with the agonist Isoproterenol, at 37 degrees but not at 4 degrees, induced a dose dependent internalization of the beta adrenergic receptor. Agonist-induced internalization was very rapid, in the order of few minutes. beta adrenergic receptor internalization was very specific: the alpha adrenergic agonist Phenylefrine had almost no effect on beta receptor levels, while Isoproterenol treatment had no effect on the number of alpha adrenergic or nicotinic receptors expressed at the cell surface of these cells. beta adrenergic receptor internalization is probably the major mechanism responsible for catecholamine desensitization in smooth muscle cells.     

Role of beta adrenoceptors in metabolic and cardiovascular responses of cold exposed humans

Effect of a nonspecific beta adrenergic blocker — propranolol (40 mg per os) on thermoregulatory responses of cold water immersed (12.5°C) humans was studied. Propranolol attenuates resting and cold induced thermogenesis, rectal temperature, heart rate and systolic blood pressure, but increases production of adrenaline and cortisol. Propranolol has no effect on the threshold body temperature for induction of cold thermogenesis and on central thermosensitivity. The following conclusions are drawn from consideration of the data presented: During the early phase of cooling (20 min after the start of cooling) the thermogenesis mediated by beta adrenergic receptors may cover about 80% of the total metabolic increase induced by cold. After about 30 min of cooling the relative proportion of beta adrenergic thermogenesis starts to decline, reaching 20% of the total cold thermogenesis at the end of cooling.

It can be suggested from consideration of the data that, in man, the beta adrenergic receptors in the heart, blood vessels, adipocytes and muscles participate in mediating effect of cold on cardiovascular and thermoregulatory responses. Furthermore, these data imply that human adrenergic thermogenesis is produced outside of the brown adipose tissue. Thus, physiological mechanisms mediating adrenergic thermogenesis in humans appear to be different from those in small mammals.     

Hydrostatic pressure and adrenergic drugs (agonists and antagonists): effects and interactions in fish

Cardiac responses to alpha and beta adrenergic drugs have been studied in the eel firstly at atmospheric pressure (1 ATA), secondly at 101 ATA per se hydrostatic pressure. The exposure of treated eels for 1 hr at 101 ATA cancels the propranolol effect, increases the clonidine effect and induces paradoxal effects (reversal effect) of isoproterenol, phentolamine and phenylephrine. The highly significant interaction (P less than 0.001) between drugs and HP at 101 ATA is discussed and interpreted as effects of hydrostatic pressure inducing a change in receptor function.     

Adrenergic versus VIPergic control of cyclic AMP in human colonic crypts

The actions of catecholamines on VIP-induced cyclic AMP is studied in human colon. We show that: (1) Epinephrine in the 10(-7)-10(-3) M concentration range (ED50 = 11.10(-6) M) inhibits VIP-induced cyclic AMP rise in isolated colonic epithelial cells; the maximal inhibition reaches 30% of VIP effect; epinephrine alters the efficacy of the peptide and does not modify its potency; epinephrine also reduces the basal cyclic AMP level. (2) The inhibition is found with other alpha adrenergic agonists with the order of potencies epinephrine greater than norepinephrine greater than phenylephrine. Clonidine has a poor intrinsic activity but antagonizes the action of epinephrine. (3) The inhibition of VIP action by epinephrine is reversed by the alpha antagonists dihydroergotamine, phentolamine and the alpha 2 antagonist yohimbine, while unaffected by the beta antagonist propranolol and the alpha 1 antagonist prazosin, (4) Epinephrine inhibits VIP-stimulated adenylate cyclase activity in preparations of colonic plasma membranes. Thus catecholamines exert through an alpha 2 adrenoreceptor a negative control on basal and VIP-stimulated cyclic AMP formation in human colon. We suggest that colonic cyclic AMP metabolism undergoes a dual control: VIPergic, activator and adrenergic, inhibitor.     

Adrenergic control of lipogenesis and lipolysis in the chicken in vitro

The adrenergic inhibition of lipogenesis and stimulation of lipolysis in the avian has been examined using chicken hepatocytes and adipose tissue explants in vitro. Lipogenesis was inhibited by adrenergic agonists: epinephrine (alpha + beta) greater than isoproterenol (beta 1/beta 2) greater than norepinephrine (alpha 1/alpha 2, beta 1) greater than metaproterenol (beta 2), phenylephrine (alpha 1). Dobutamine (beta 1 agonist) and dopamine (dopaminergic agonist) did not significantly affect [14C]acetate incorporation into lipid, while clonidine and para-aminoclonidine (alpha 2 agonists) were slightly stimulatory. Lipolysis in young and adult chicken adipose tissue was stimulated by epinephrine, isoproterenol, phenylephrine, dobutamine and metaproterenol, but was inhibited by clonidine and para-aminoclonidine. Both the antilipogenic and lipolytic effects of epinephrine were partially blocked by phentolamine (alpha 1 = alpha 2 antagonist) or propranolol (beta 1 = beta 2 antagonist), but completely inhibited by phentolamine and propranolol administered together.     

Cerebrovascular smooth muscle culture. II. Characterization of adrenergic receptors linked to adenylate cyclase

Cultured and propagated smooth muscle cells contain adenylate cyclase (AC) responsive to catecholamines and their analogues. Isoproterenol and zinterol were the most effective stimulants of AC activity with EC50 = 8.5 X 10(-8)M. They were followed by epinephrine, phenylephrine and norepinephrine (EC50 = 7.5 X 10(-7)M, 6.5 X 10(-6)M and 4 X 10(-6)M, respectively). When the selective antagonists for beta 1 and beta 2 receptors (beta 1-type practolol and atenolol, beta 1/beta 2-type propranolol and beta 2-type butoxamine) were tested against isoproterenol, epinephrine and norepinephrine stimulation of AC activity, the beta 1 in contrast to beta 2 antagonists were found ineffective. The alpha-blockers (phentolamine alpha 1/alpha 2-type antagonists) and yohimbine (alpha 2-type antagonist) alone or in the presence of propranolol did not significantly inhibit the catecholamine-induced enhancement of cAMP formation. On the other hand, prazosine (alpha 1-type antagonist) blocked the stimulatory effect of epinephrine and norepinephrine on AC system. Similarly, the alpha 2-agonist, clonidine, did not affect the catecholamines' stimulated AC activity while alpha 1 agonist, phenylephrine, induced an additive enhancement of norepinephrine production of cAMP. The findings of beta-2- and alpha-1-type adrenergic receptors in the cultured cerebrovascular smooth muscle provide additional support for the implicated involvement of adrenergic innervation in the regulation of cerebral blood flow and/or systemic blood pressure.