Thiol reactivity and the molecular individuality of alpha- and beta-adrenoreceptors in rat liver plasma membranes.

Whether or not alpha- and beta-adrenoreceptors are non-identical binding sites on the same protein is still an open question. We investigated the effects of sulfhydryl reagents and dithiothreitol on the binding of [3H]dihydroalprenolol and [3H]dihydroergocryptine to beta- and alpha-adrenoreceptors of rat liver plasma membranes. Dithiothreitol inhibited the binding of [3H]dihydroalprenolol to the beta-adrenoreceptor, whereas it had no effect on the specific binding of [3H]dihydroergocryptine to the alpha-adrenoreceptor. In contrast, mersalyl, a mercurial SH reagent, readily blocked the alpha-adrenoreceptor and, although to a lesser extent the beta-adrenoreceptor. The interaction of mersalyl with the alpha-adrenoreceptors was almost instantaneous. In contrast, under the same experimental conditions, the inactivation of the beta-adrenoreceptors was much slower (t 1/2 : 7 min). Finally, a marked difference in the accessibility of the SH groups to mersalyl was observed between the alpha- and beta-adrenoreceptors. The presence of 15 microM (-)-epinephrine or 1.5 microM phentolamine was sufficient to prevent the blockade of the alpha-adrenoreceptor by mersalyl, but inactivation of the beta-adrenoreceptor by mersalyl was not modified by 500 microM (-)-epinephrine and was only slightly decreased by 50 microM (-)-propranolol. Thus, the alpha- and beta-adrenoreceptors from rat liver plasma membranes exhibited biochemical differences which may be interpreted in favor of their molecular individuality.     

Participation of the alpha- and beta-adrenoreactive systems of the brain in the regulation of contractile thermogenesis in the cat]

The influence of intraventricular injections of alpha- and beta-adrenergic substances (mesaton, phentolamine, isadrin, and propranolol) was investigated in cats. It was found that the central alpha-adrenoreceptors were involved in the shivering activating system and beta-adrenoreceptors -- in the inhibitory one.     

Adenylate cyclase and adrenoreceptors in the myometrium

Data are presented on the content and hormonal regulation of alpha- and beta-adrenoreceptors in myometrium, interrelation of adrenoreceptors with adenylate-cyclase and contractile state of myometrium. Processes in the structure of adenyl-cyclase complex during the enzyme desensitization have been discussed.     

Mitotic activity of regenerating rat liver following stimulation with alpha- and beta-adrenoreceptors

A study was made of the effect of stimulating alpha- and beta-adrenoreceptors on the mitotic activity of the rat regenerating liver following resection. Mesaton, a stimulator of alpha-adrenoreceptors, and isadrin, a stimulator of beta-adrenoreceptors, in a dose of 0.2 mg/kg were injected one hour before liver resection or 30 min, 8 and 24 h after operation. In all experimental groups, mesaton gave rise to an increase in the mitotic index without lowering the coefficient of the mitotic phases. The least pronounced stimulating effect was attained when mesaton was injected 9 hours after partial hepatectomy. Isadrin reduced the mitotic activity as judged from the decrease of the coefficient of the phases and augmentation of the number of binuclear cells. The experiments confirmed a previously advanced assumption that stimulation of alpha-adrenoreceptors favours while that of beta-adrenoreceptors reduces cell proliferation.     

Role of alpha- and beta-adrenoreceptors in isolated guinea pig trachea anaphylaxis to aerosol tick (D. pteronyssinus) allergy

Experiments were performed on inhalation-sensitized guinea-pigs, with the use of immunoallergic neurohistochemical techniques. Anaphylactic tracheobronchial spasm was shown to be related not only to the degree of sensitization but also to the state of alpha- and beta-adrenoreceptors. Sensitization, in its turn, changed the function of adrenoreceptors. It increased histamine sensitivity and decreased catecholamine sensitivity of an isolated organ.     

Study of the stimulating effect of the sympathetic stem on the stomach contraction

Stimulation of the sympathetic stem chest portion induces enhancement rather than suppression of gastric contractions. The activating effect is more obvious under conditions of the alpha- and beta-adrenoreceptors blockade with phenolamine and obsidan, and eliminated with the smooth muscle serotoninoreceptors blocking agent lisergol. The findings suggest that the sympathetic stem includes some serotoninergic neural fibres exerting a strong effect upon gastric and intestinal contractions. A previously unknown serotoninergic part of the vegetative nervous system controlling the internal organs functions, seems to exist in the organism.     

Adrenergic receptors in human fetal liver membranes

The adrenergic receptor binding capacities in human fetal and adult livers were measured to investigate the mechanism of the reduced alpha-1 adrenoreceptor response of the liver associated with a reciprocal increase in beta-adrenoreceptor activity in a number of conditions. Alpha-1 and beta-adrenoreceptor density were determined using 3H-prazosin and 3H-dihydroalprenolol, respectively, as radioligand. Heterogenous populations of beta-adrenoreceptors were found in fetal liver contrast to adult. Decreased alpha-1 and increased beta-receptor density were found which may relate to a decreased level in cellular differentiation. These findings may be important for the investigation of perinatal hypoglycaemia of newborns after treatment of premature labour with beta-mimetics. This is the first demonstration of differences in the ratio of alpha-1 and beta-adrenoceptors in human fetal liver.     

The short-term and long-term effects of gamma-irradiation on the inotropic reaction of the myocardium during the activation of alpha- and beta-adrenoreceptors

The contractile function of myocardium was impaired and its inotropic response to stimulation of alpha- and beta-adrenoreceptors decreased at early times (1-30 days) following whole-body gamma-irradiation with a dose of 1.0 Gy. Six months after irradiation the response of the isolated myocardium to stimulation of adrenoreceptors increased to exceed that of intact animals. In a year the reactivity of the myocardium towards alpha-adrenoreceptor agonists remained high and its sensitivity of phenylephrine hydrochloride increased considerably; the response to beta-adrenoreceptor agonists was virtually absent.     

Beta-adrenergic receptor blockade during exercise decreases intestinal lymphocyte apoptosis but not cell loss in mice

Catecholamines induce apoptosis in various lymphoid populations. This process can occur with both alpha- and beta-adrenoreceptors. Heavy exercise increases plasma catecholamine concentrations, and is also a cause of lymphocyte apoptosis, a possible explanation for postexercise lymphocytopenia. The purpose of this study was to examine the effects of adrenoreceptor antagonism on exercise-induced decreases and apoptosis of intestinal lymphocytes. Mice received an intraperitoneal injection of phentolamine (a nonselective alpha-blocker), nadolol (a nonselective beta-blocker), or saline (vehicle) prior to an exhaustive bout of exercise. Total intestinal lymphocyte numbers, percent and number of CD3+ lymphocytes, and cell viability were assessed. Neither alpha- nor beta-antagonism prevented exercise-induced cell loss in the intestine; however, pretreatment with nadolol significantly reduced the number of apoptotic and necrotic cells. Phentolamine administration appeared to increase the incidence of cell death among intestinal lymphocytes. Both drugs decreased the percentage of CD3+ intestinal lymphocytes. Our study suggests that catecholamines are not responsible for postexercise lymphocytopenia, but beta-adrenoceptor blockade may confer protection against exercise-induced apoptosis of intestinal lymphocytes.     

Role of adrenergic structures in regulating the release by the intestines of hemocoagulating compounds into the blood stream

Experiments on cats were made to study the capability of adrenaline, tropaphen and propranolol of influencing the intensity of the release of hemocoagulating compounds and anticoagulants from the intestinal vessels and tissues to the bloodstream (perfusate). Adrenaline was found to increase the coagulative activity of the perfusate, provoking an enhanced release into it of thromboplastin, an analogue of plasma factor V and antiheparin compounds and suppressing the release of antithromboplastins. The blockade of the alpha-adrenoreceptors was accompanied by a dramatic increase of antithromboplastins to the intestinal perfusate, whereas the depression of the activity of beta-adrenergic structures by reduction of the release of tissue thromboplastin inhibitors. It is concluded that regulation of the release of antithromboplastins in the intestine is mediated by the structures similar in their characteristics to alpha- and beta-adrenoreceptors.     

Possible role of somatotropic hormone in regulating the functional state of glial cells in the central nervous system

Experiments were made to study the actions of STH and its fragment capable to stimulate the growth processes on MAO activity and selective binding of catecholamines by alpha- and beta-adrenoreceptors in glial cells of the rat brain cortex. For comparison the effects of STH and its fragment on 3H-PGE1 binding were studied. STH and its fragment were found to produce no influence on MAO activity or specific binding of 3H-PGE1 with glial cells. STH and its fragment (5.10(-9) M) were found to reduce specific binding of 3H-dihydroergocryptine with beta- and alpha-adrenoreceptors of glial cells, respectively. It is suggested that STH and its fragment can modulate the function of glial cells by changing the selective action of catecholamines on subpopulations of adrenergic receptors.     

Effects of thyroid hormones and reverse-triiodothyronine (rT3) pretreatment on beta-adrenoreceptors in the rat heart

Effects of thyroxine (T4), triiodothyronine (T3) or reverse-triiodothyronine (rT3) in vivo pretreatment or the effect of hypothyroidism on properties of beta-adrenoreceptors in the rat heart were investigated. beta-adrenergic antagonist hydroxybenzylpindolol (HYP125I) was used to estimate the maximal binding capacity (MBC) and the affinity (KD) of beta-adrenoreceptors. Both T4 and T3 in dose and time dependent manner increased MBC value but only slightly and insignificantly affected affinity of the beta-adrenoreceptor. The effect of T3 on MBC was higher than that of an equal dose of T4, but the latter effect persisted longer than that of T3. Hypothyroidism decreased MBC value, but increased the affinity of beta-adrenoreceptors. Pretreatment of rats with rT3 produced changes in beta-adrenoreceptors similar to those seen in hypothyroid rats.     

The role of adrenoreceptors in the mechanism of pharmacological action of cavinton

Having studied the functional state of beta-adrenoreceptors in vitro by the radioligand (3H-dihydroalprenalol) method it has been shown that cavinton in the concentration of 2.5 X 10(-6) M considerably increases the affinity of beta-adrenoreceptors for the ligand. In the in vivo experiments on rats the intraperitoneal injection of cavinton in the dose of 2 mg/kg causes an increase in the affinity of synaptosomal beta-adrenoreceptors for the ligand 10 days after chronic administration without altering the concentration of the receptors (Bmax) themselves. 20 days after the injection of the drug the affinity still grows and this effect of cavinton is retained even 30 days after the injection.     

The effect of catecholamines on blood circulation in the liver

In acute experiments on dogs under nembutal anaesthesia the pressure and blood flow in the vessels supplying the liver have been recorded simultaneously with registration of the hepatic blood content changes. Catecholamines injected into liver vessels have been found to change significantly the liver circulation: adrenaline and noradrenaline evoke the constriction of intrahepatic vessels and decrease the blood content in the liver, realising through the alpha-adrenoreceptors activation, isadrin causes a weak vasodilatation by the activation of beta-adrenoreceptors. A selective inactivation of isadrin in the liver is shown. The density of alpha-adrenoreceptors distribution in the intrahepatic vessels is large enough and apparently some times exceeds the density of beta-adrenoreceptors. In 1/3 of dogs the beta-adrenoreceptors in the liver vascular bed are absent at all or present in arterial bed only.     

Effect of beta-adrenoreceptor stimulation on gastric secretion stimulated by histamine, acetylcholine, and pentagastrin

In chronic experiments on dogs with gastric and duodenal fistulas and catheters implanted into the jugular vein, it was established that the beta-adrenoagonist novodrin inhibits gastric secretion stimulated with acetylcholine or pentagastrin but does not alter secretion stimulated with histamine. The inhibitory effect of novodrin on gastric secretion is a consequence of its direct action on beta-adrenoreceptors of the gastric mucosa. The scheme demonstrating interrelations of beta-adrenoreceptors to acetylcholine, gastrin and histamine is offered.     

The pulmonary hemodynamic changes under experimental myocardial ischemia in rabbits following beta-adrenoreceptors blockade

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied as well as in control animals and after the blockade of beta-adrenoreceptors. The myocardial ischemia decreased the left ventricular myocardial contractility, cardiac output and arterial pressure, decreased the pulmonary artery pressure and flow. Following myocardial ischemia, the pulmonary artery pressure decreased less than pulmonary artery blood flow as the result of elevating of the left atrial pressure, meanwhile pulmonary vascular resistance was not changed. Following myocardial ischemia in animals after the blockade of the beta-adrenoreceptors, the pulmonary flow decreased the same as in control animals. However, the pulmonary artery pressure was decreased twofold more significantly than in control animals, and its diminishing was in the same degree as the pulmonary artery flow. Following myocardial ischemia after the blockade of the beta-adrenoreceptors, the pulmonary vascular resistance decreased whereas the left atrial pressure did not change significantly because the myocardial contractility decreased less than in control animals.     

Changes in the density of human lymphocyte beta-adrenergic receptors in hypertension

The beta-adrenoreceptor density in intact lymphocytes of peripheral blood of normotensive and hypertensive adults was measured by the radioligand binding technique with the use of 3H-dihydroalprenolol. The density of beta-adrenoreceptors was found to be higher in lymphocytes of hypertensive subjects while the number of the receptors was equal to 2076 +/- 208 and 1461 +/- 175 receptors per cell, respectively, in hypertensive and normotensive subjects. The dissociation constants in both cases varied from 0.4 to 1.8 nM. Probably, the decreased responses to the adrenergic agents in hypertensive subjects are not connected with the decreased number of beta-adrenoreceptors and may be due to alterations in postreceptor events.     

Comparative study of beta-adrenoreceptors of rat brain synaptic membranes

Affinity of beta-adrenoreceptors in the rat brain synaptic membranes to agonists isoproterenol and norepinephrine, as well as to antagonist 125I-hydroxybenzylpindolol is lower in young (1 month) and old (24--26 months) than in mature (8--12 months) rats. Desensitization toward isoproterenol is expressed in the young ones only. In the old but not in other groups simultaneous action of isoproterenol and N-ethylmaleimide decreases the following binding of the antagonist while the same agents added separately produced no effect. It is suggested that beta-adrenoreceptors undergo age-related changes in their conformational state due to modification of the membrane environment.     

Desensitization of beta-adrenoreceptors and its influence on manifestations of the antiradiation effect of isoproterenol

A study was made of the function of beta-adrenoreceptors and Chinese hamster fibroblast cAMP during their desensitization to isoproterenol. Desensitization of adenylate cyclase was demonstrated to lead to the reduction of both the cAMP response to isoproterenol and isoproterenol capacity to protect the cells from ionizing radiation. This did not entail any changes in the number of beta-adrenoreceptors or in the dissociation constant of the beta-antagonist. It is assumed that desensitization provokes functional dissociation of the beta-receptor and adenylate cyclase. Intact adenylate cyclase is an absolute must for realization of the antiradiation potency of isoproterenol.     

Synchronization of secretion of the evoked transmitter quanta as mechanism of the facilitating action of sympathomimetics

Noradrenaline, isoproterenol, dobutamine were found to modulate kinetics of quanta secretion so as to synchronize the transmitter release. This effect could be prevented with blocking agents of beta-adrenoreceptor (atenolol, propranolol). Activators of beta-adrenoreceptors klonidine and phenylephrine did not change the kinetics of quanta secretion, whereas phentolamine did not affect the synchronizing effect of noradrenaline. The change in the time course of the secretion induced by noradrenaline increased the end-plate current amplitude. There seems to exist a specific presynaptic mechanism involving beta-adrenoreceptors for facilitation of effects of sympathomimetics.