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At least 1,081 records · Page 60Linked to original sources
PubMed1988

Alpha 2-adrenergic receptors in brown adipose tissue of infant rats--I. Identification and characteristics of binding sites in isolated plasma membranes.

1. Alpha 2-Adrenoceptor antagonists [3H]yohimbine and [3H]RX 781094 and the partial alpha 2-agonist [3H]clonidine exhibited specific binding to plasma membrane fragments isolated from interscapular brown fat of 7-day-old rats. 2. Competition studies with epinephrine, yohimbine and practolol revealed that [3H]norepinephrine, the principal in vivo agonist acting upon brown adipocytes, can readily bind to alpha 2-adrenoceptors in brown fat of infant rats. 3. The presence of alpha 2-adrenoceptor subclass in brown fat of infant rats may play a role in the sympathetic regulation of this rapidly proliferating tissue.

Adipose Tissue, Brown↗
PubMed1984

A fundamental temperature-dependent difference between beta-adrenoceptor agonists and antagonists.

Positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to sympathomimetic amines were examined at bath temperatures of 38, 30 or 25 degrees C. The concentration-response curves to isoproterenol and orciprenaline were displaced to the left by cooling, indicating hypothermia-induced supersensitivity. The affinities of isoproterenol and orciprenaline were determined as their dissociation constants (pKA) from antagonism of their responses by either the functional antagonist carbachol or Ro 03-7894 which is reported to be an irreversible beta-adrenoceptor antagonist. By both methods of calculation, the affinities of isoproterenol and orciprenaline for the beta-adrenoceptors mediating inotropic and chronotropic responses were increased by lowering the temperature. In contrast, the affinity of practolol, measured as the pA2 for competitive antagonism of the isoproterenol- and orciprenaline-induced inotropic and chronotropic responses, did not increase with cooling. Thus hypothermia-induced supersensitivity is associated with an increase in agonist affinity only, which indicates a fundamental temperature-dependent difference between agonist and antagonist interactions with the beta-adrenoceptor.

Animals↗
PubMed1984

Interaction of alpha adrenergic antagonists with calmodulin.

Several alpha-adrenergic antagonists inhibited the activation of calmodulin-stimulated phosphodiesterase at concentrations that had little or no effect on basal phosphodiesterase activity. The most potent of these compounds were phenoxybenzamine and dibenamine (IC50 values of about 1 microM); the amino acid ergot alkaloids ergocryptine, ergocristine, ergotamine and their dihydrogenated derivatives were less potent calmodulin-inhibitors (IC50 values of 35-80 microM). The amino ergot alkaloids ergonovine and methysergide were essentially devoid of inhibitory activity. A variety of other alpha 1-antagonists (phentolamine, tolazoline and prazosin), an alpha 2-antagonist (yohimbine), alpha-agonists (norepinephrine, phenylephrine and clonidine), beta-adrenergic antagonists (propranolol and practolol) and the beta-adrenergic agonist methoxyphenamine displayed little or no anti-calmodulin activity (IC50 values greater than 300 microM). Similarly, the alkylating agents chlorambucil and mechlorethamine also failed to inhibit calmodulin activity. Phenoxybenzamine and dibenamine inhibited calmodulin activity irreversibly, whereas the inhibition caused by other alpha adrenergic blocking agents was reversible. Phenoxybenzamine inhibited calmodulin activity by binding directly to it. This binding was calcium-dependent and irreversible. The irreversible binding and inhibition of calmodulin activity by phenoxybenzamine (or dibenamine) may serve as a useful tool for studying the sites at which drugs bind to calmodulin and may also be useful for studying the distribution and turnover of calmodulin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

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.

Adenylyl Cyclases↗
PubMed1984

Testosterone control of brain and anterior pituitary beta-adrenergic receptors.

Orchidectomy of adult albino rats resulted in a quick, (approximately 70%) increase in the density of beta-adrenergic receptors in the anterior pituitary gland within the first day. There was a concurrent rapid increase in plasma levels of pituitary gonadotropins. The beta-receptor density continued to increase slowly for at least 16 days after castration, but it could be lowered significantly to the levels of sham-operated animals by treatment with testosterone (3 mg/kg/day) beginning on the fourth day after castration and continuing for 4 days. This treatment also completely reversed the elevation in plasma levels of luteinizing hormone (LH), and significantly reduced the circulating follicle-stimulating hormone (FSH) levels. Prolactin levels were not significantly altered by the treatments used in these studies. Most of the beta-adrenergic receptors induced by orchidectomy in the anterior pituitary were shown, using a beta 1-selective antagonist, practolol, or a beta 2-selective antagonist, IPS-339, to be of the beta 2-subtype. The density of the beta-adrenergic receptors in the cerebral cortex also increased significantly (10-24%) after castration, and returned to the levels of sham-operated animals following treatment with testosterone. No significant change in the density of the beta-adrenergic receptors in the hypothalamus resulted from either castration or testosterone replacement.

Animals↗
PubMed1995

Novel evidence that beta adrenoceptors of the medial septal area regulate blood pressure and electrolyte balance.

We investigated the participation of the beta-adrenoceptors of the septa area (SA) in sodium and potassium excretion and urine flow. The alterations in arterial pressure and some renal functions were also investigated. The injection of 2.10(-9) to 16.10(-9) M of isoproterenol, through a cannula permanently implanted into the SA produced a significant dose-dependent decrease in urinary Na+ and K+ excretion and urinary flow. Pretreatment with 16.10(-9) M butoxamine antagonized the effect of 4.10(-9) M isoproterenol but pretreatment with 16.10(-9) M practolol did not abolish the effect of isoproterenol. The beta 2-agonist terbutaline and salbutamol (4.10(-9) M when injected intraseptally also caused a decrease in urine flow and in renal Na+ and K+ excretion. After injection of isoproterenol or salbutamol (4.10(-9) M) into the SA, the arterial pressure, glomerular, filtration rate (GFR) and filtered Na+ were reduced while Na+ fractional reabsorption was increased. The results indicate that the beta 2-adrenoceptors of the SA play a role in the decrease of Na+, K+ and urine flow and this effect may be due to a drop in GFR and filtered Na+ and to the rise in tubular Na+ reabsorption.

Animals↗
PubMed1983

Adenylate cyclase sensitivity to catecholamines and forskolin in rat pia-arachnoid and cerebral microvessels.

Adenylate cyclase in homogenates of perfused pia-arachnoid from the rat brain displayed a sensitivity for activation by dl'isoproterenol, l'epinephrine, l'norepinephrine (NE) and fenoterol that was greater than shown by partial beta2 adrenergic agonists (metaproterenol and salbutamol), or partial beta1 adrenergic agonists (tazolol and dobutamine) and an alpha adrenergic agonist (phenylephrine). The addition of the quanosine triphosphate (GTP) analog, Gpp(NH)p(5'-guanylyl imidodiphosphate) to the enzyme preparations resulted in an increased ability of all agents (except tazolol) to activate adenylate cyclase. The agent, forskolin, exerted a very potent activation of the catalytic site of adenylate cyclase in both pia-arachnoid and cerebral microvessels (capillary fraction). The order of potency for adrenergic antagonists to inhibit NE-induced stimulation of the pial enzyme was: propranolol (mixed beta) greater than butoxamine (beta2) greater than phentolamine (alpha1) greater than practolol (beta1). Subchronic injections of reserpine to rats resulted in a pial enzyme that was hyper-responsive to NE and isoproterenol. Similarly, the capillary enzyme displayed an enhanced activity to NE and dopamine (DA). Both high and low Km forms of cyclic AMP (cAMP) phosphodiesterase were detected in developing and adult pia-arachnoid and capillaries. The addition of a calmodulin fraction plus calcium ions did not elicit activation of the high Km enzyme. Moreover, adenylate cyclase during development was sensitive to activation by NE and forskolin. Thus, the pia-arachnoid possesses an adenylate cyclase receptor-coupled system with a mixed response to catecholamines, but which is primarily beta2 in nature. In addition, this system, as well as the capillaries, possesses a capacity to respond to manipulation of monoamine levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Monoamine activation and enkephalin inhibition of adenylate cyclase in dorsal and ventral striatum of the rabbit.

Adrenergic-sensitive adenylate cyclase was found to be present in the nucleus accumbens and ventral caudate of the rabbit, but displayed less activity in the dorsal caudate. In general, stimulation of the enzyme by dopamine (DA) was most sensitive to inhibition by fluphenazine while norepinephrine (NE)-stimulated activity was highly sensitive to both fluphenazine and propranolol. Other selective adrenergic-receptor blocking agents (butoxamine, practolol, yohimbine and prazosine) were more effective in antagonizing the effect of NE as opposed to DA-activation. Activation of adenylate cyclase by NE in the dorsal caudate displayed less sensitivity to these adrenergic antagonists than in the other two areas. Horseradish peroxidase-positive cells were present in the locus coeruleus, following injection into the nucleus accumbens. Activity of basal and guanosine triphosphate (GTP)-sensitive adenylate cyclase was reduced by enkephalins in these three brain regions. This action was reversed by naloxone. Met-enkephalin did not affect either NE- or DA-mediated responses in any area.

Adenylyl Cyclase Inhibitors↗
PubMed1988

[3H]glycogenolysis in brain slices mediated by beta-adrenoceptors: comparison of physiological response and [3H]dihydroalprenolol binding parameters.

The subclass of beta-adrenergic receptors mediating glycogenolysis in slices from cerebral cortex of the mouse, incubated in the presence of [3H]glucose, was identified by comparing the relative potencies of agonists and the inhibition constants of antagonists to those found on reference systems. (+/-)Isoprenaline, (-)adrenaline and (-)noradrenaline produced a concentration-related glycogenolysis with Kact values of 2.2 x 10(-8) M, 2.8 x 10(-7) M and 3.6 x 10(-7) M, respectively. Zinterol, a selective beta 2-adrenergic agonist, did not produce any glycogenolytic response even in a large concentration. Salbutamol, a predominantly beta 2-adrenergic receptor agonist, elicited in a very large concentration (10(-4) M) less than 40% glycogenolysis, an effect which was not related to stimulation of beta-adrenergic receptors. The predominantly beta 1-adrenergic receptor antagonists, practolol and metoprolol shifted the concentration-response curve to noradrenaline to the right, with apparent Ki values of 8.0 x 10(-7) M and 7.6 x 10(-8) M, respectively, close to those reported in the rat heart. These various data indicate that the glycogenolytic response is selectively mediated by beta 1-adrenergic receptors. Under experimental conditions which were strictly identical to those used to measure glycogenolysis, a saturable binding of [3H]dihydroalprenolol to the slices occurred with Kd and Bmax values consistent with corresponding values on cell free preparations. Whereas the Ki values of antagonists were similar on the two systems, the Kact values of agonists on glycogenolysis were 10 times less than the Ki values for the binding of [3H]dihydroalprenolol. This suggests that the maximal glycogenolytic response is elicited for a partial receptor occupancy.

Animals↗
PubMed1979

Lung compliance and cholesterol during stellate ganglion stimulation.

The relationships between lung compliance, surface tension, and cholesterol during stimulation of the sympathetic nervous system were studied in 28 cats. Cats were anesthetized with ketamine hydrocholoride, injected with one of five sympathetic blocking agents or inhibitors and injected with isoprotenol. The left stellate ganglion was then stimulated electrically for 5 min. We found that stimulation decreased lung compliance and increased the surface tension and the cholesterol concentration in the lung wash fluid. Alpha blockers (phentolamine and phenoxybenzamine) and catecholamine inhibitors (reserpine and guanethidine) prevented these changes, but the beta blocker practolol did not. In additional experiments airway resistance, functional residual capacity and lung weights did not change during stellate stimulation. The results from the present study suggest that stellate ganglion stimulation resulted in decreased lung compliance with an increased surface tension and cholesterol in lung wash fluid.

Animals↗
PubMed1976

Reduction by propranolol of raised urinary output of MHPG in hyperactive rats.

Prolonged isolation of rats resulted in hyperactivity in the open field and a significant increase in 24 hr urinary excretion of MHPG (3-methoxy-4-hydroxyphenylglycol). Exploratory activity of group-housed rats in open field was not associated with raised MHPG excretion, compared with that of rats remaining in home cages. Exposure of group-housed rats to 4 degrees C for 2 hr also increased urinary excretion of MHPG. Pretreatment of isolated rats with dl-, d-propranolol or practolol abolished hyperactivity of isolated rats and reduced MHPG output in these rats and in rats exposed to cold. dl-Propranolol did not reduce activity of group-housed rats in open field or their urinary excretion of MHPG. It is suggested that propranolol may have a selective inhibitory effect on stress-induced increases in noradrenaline turnover.

Animals↗
PubMed1986

Nicotine-induced convulsions in cats and central nicotinic receptors.

The effects were investigated of intracerebroventricular (ICV) injections in the cat of ganglionic blocking agents, antimuscarinic drugs, alpha and beta adrenergic blocking substances, dopamine antagonists, an antihistamine, reserpine and a 5-hydroxytryptamine antagonist as well as the inhibitors of catecholamines, 5-hydroxytryptamine and acetylcholine synthesis upon convulsions produced by nicotine, which was similarly injected. Mecamylamine and hexamethonium but not atropine, scopolamine, yohimbine, phenoxybenzamine, tolazoline, propranolol, practolol, chlorpromazine, haloperidol, antazoline and methysergide abolished the convulsions evoked by nicotine. Furthermore, reserpine, but not 6-hydroxydopamine, as well as 5,6-dihydroxytryptamine and hemicholinium blocked the convulsions caused by nicotine. It appears, therefore, that the convulsions produced by nicotine are mediated through central nicotinic receptors. However, the depressed catecholaminergic, 5-hydroxytryptaminergic and histaminergic mechanisms induced by reserpine can also suppress the convulsions evoked by nicotine.

5,6-Dihydroxytryptamine↗
PubMed1986

6-Hydroxydopamine-induced aggression in cats: effects of various drugs.

The effects of intracerebroventricular injections (ICV) in the unanesthetized cat of antimuscarinic drugs, ganglionic blocking agents, alpha and beta adrenergic blocking substances, dopamine and 5-hydroxytryptamine (5-HT) antagonists, and an antihistamine on aggressive behavior produced by 6-hydroxydopamine injected similarly was investigated. It was found that atropine, hyoscine, hexamethonium, mecamylamine, yohimbine, phenoxybenzamine, propranolol, practolol, chlorpromazine, haloperidol, antazoline and methysergide exerted virtually no effect on the pattern of aggressive responses evoked by ICV 6-hydroxydopamine. It is thus concluded that the aggressive behavior induced by 6-hydroxydopamine is not related to the release of acetylcholine, norepinephrine, dopamine, histamine or 5-hydroxytryptamine from endogenous storage sites in the brain.

Aggression↗
PubMed1976

The effect of pertussis and beta adrenergic-blocking agents on mast cells.

Pertussis vaccine injected ip in doses known to cause hypersensitization resulted in a marked decrease in the number of mast cells from the peritoneal washings of rats and mice. A significant reduction was obtained as early as one day after pertussis injection of ten billion cells in rats and was marked after 5 to 7 days. A maximum reduction in the number of mast cells was obtained by a dose of 20 billion cells. There was no detectable histamine biological activity in the supernatant from peritoneal washings obtained after 10 min, 60 min, and 24 hr from control and pertussis-treated rats, indicating that pertussis did not cause degranulation of mast cells in vivo. The histamine content in the precipitated mast cell pellets from control rats was much higher than the corresponding histamine content from pertussis-treated rats. In rats and mice, propranolol and other beta adrenergic-blocking agents caused degranulation of mast cells in the peritoneal washings in vitro. Practolol was the least effective beta adrenergic-blocking agent in degranulating mast cells. Catecholamines, histamine, 6-hydroxydopamine, methacholine, and pertussis failed to cause any degranulation. Isoproterenol protected the mast cell against the degranulation induced by propranolol. Propranolol caused bluing in rat and mice skin when injected id. Mast cells from control and pertussis-injected rats were equally sensitive to propranolol in vitro. The low recovery of mast cells from the peritoneal washings of rats and mice is thought to be due to mobilization of mast cells away from the peritoneum.

Adrenergic beta-Antagonists↗
PubMed1982

Electrophysiological and cyclic AMP responses to beta-adrenergic receptor stimulation and catecholamine levels in cat and rabbit sympathetic ganglion.

The effects of beta 1- and beta 2-selective and nonselective adrenergic agonists and antagonists were studied in the cat and rabbit superior cervical ganglion (SCG) in situ and in vitro. In experiments on the cat SCG in situ beta-adrenergic agonists induced an increase in positive afterpotential (PAP) of compound ganglionic action potential evoked by preganglionic stimulation in the following order of potency: isoprenaline (ISO) greater than salbutamol much greater than tazolol. Beta-adrenergic antagonists inhibited the ISO response in the following order of potency: propranolol greater than exaprolol much greater than H 35/25. Practolol did not exhibit beta-adrenergic blocking action; on the contrary, in higher doses it enhanced the response to ISO. In higher doses all beta-adrenergic antagonists tested depressed ganglionic transmission in an approximately similar range of doses. In experiments in vitro, using sucrose-gap technique. ISO induced depolarization of the cat SCG and this effect was inhibited in a dose-dependent manner by propranolol. Beta-adrenergic agonists did not induce depolarization of the rabbit SCG in experiments in situ and in vitro. The level of noradrenaline and dopamine in the cat and rabbit SCG did not differ significantly. Low level of adrenaline was found in the cat SCG; however, no adrenaline was detected in the rabbit SCG. No statistically significant change of cyclic AMP content was observed in the cat and rabbit SCG or in the incubation medium under conditions similar to those in which ISO induced depolarization of the cat SCG. It is concluded that the beta-adrenergic receptors present in the cat SCG resemble the beta 2-subtype and that the presence of an electrophysiologic response to beta-adrenergic agonists appears to be species-dependent. The depolarization of the cat SCG due to beta-adrenergic receptor stimulation is not coupled with cyclic AMP increase.

Action Potentials↗
PubMed1983

Biogenic amines and adenosine-sensitive adenylate cyclases in primary cultures of striatal neurons.

Primary cultures of virtually pure striatal neurons from 16-day-old mouse embryos can be obtained using a serum-free chemically defined medium. Membranes prepared from these cells contain dopamine, beta-adrenergic, serotonin and adenosine sensitive adenylate cyclases. The pharmacological properties of the dopamine receptors are similar to those found for D1 receptors in adults except for the apparent affinities for agonists which were 5-10 times higher in fetal neurons. Beta-adrenergic receptors of striatal and cerebellar fetal neurons are of the beta 1-subtype as indicated by their identical affinity for adrenaline and noradrenaline and by their homogeneous, high affinity for practolol (Ki = 1.3 X 10(-6)M). Adenosine and serotonin sensitive adenylate cyclases present classical characteristics. An extensive study of the additive effects of the 4 neurotransmitter-sensitive adenylate cyclases indicates that: (1) part of the neurons bear more than one type of biogenic amine receptors; (2) the serotonin receptors are always associated with adenosine receptors on the same neurons; (3) adenosine- and dopamine-sensitive adenylate cyclases are additive. From this it can be concluded that as far as their adenylate cyclases-linked amine receptors are concerned, a maximal number of 15 types of neurons are present in these striatal cell cultures.

Adenosine↗
PubMed1984

Stimulation of beta 2-adrenergic receptors suppresses sterol synthesis in human mononuclear leukocytes.

The beta-adrenergic receptor mediating the inhibition of sterol synthesis by catecholamines in freshly isolated human mononuclear leukocytes was defined pharmacologically by using selective beta 1- and beta 2-agonists and -antagonists. Incubation of cells for 6 h in a medium containing lipid-depleted serum resulted in a 3-fold increase in the incorporation of [14C]acetate or tritiated water into sterols. The beta-agonist (-)-isoproterenol was approximately equipotent with (-)-epinephrine and (-)-norepinephrine in suppressing sterol synthesis, yielding a sigmoidal log-dose-effect curve. Accordingly, the effects of the catecholamines were reversed by the beta-antagonist (+/-)-propranolol. The beta 2-agonists terbutaline and salbutamol inhibited sterol synthesis by 42 and 26%, respectively, at a concentration of 0.1 mmol/l. Contrary to that, the beta 1-agonists prenalterol and dobutamine had no effect. In accordance with the influence of the agonists, the beta 2-antagonist butoxamine, but not the beta 1-antagonists atenolol, metoprolol and practolol, reversed the catecholamine action on sterol synthesis. The results provide evidence that catecholamines may regulate sterol synthesis by stimulating beta 2-adrenergic receptors.

Adrenergic beta-Agonists↗
PubMed1979

Lethal synergism between morphine or other narcotic analgesics and propranolol.

Interactions of (+/-)-propranolol HCl with various narcotics were determined in albino rats. The 24-h intraperitoneal (i.p.) LD50 of morphine sulfate + saline was 15--16 times greater than for morphine + propranolol in both sexes although morphine was nearly twice as toxic to males as to females. The potency ratios for LD50's with saline vs. with propranolol were: codeine, 1.9, (+/-)-methadone, 6.0; (-)-alpha-acetylmethadol, 2.8 (72 h). The toxicity of levorphanol also was greatly increased with propranolol, but the dose-effect relationship showed non-parallelism vs. levorphanol + saline. Albino mice and mongrel dogs also showed synergism between morphine and propranolol. Mortality after morphine and propranolol was antagonized by naloxone or naltrexone in rats and mice. The potency ratio in rats for morphine + saline vs. morphine + practolol was 3.5. However, the synergism between propranolol and the narcotics probably was unrelated to beta-adrenergic blocking effects of propranolol because of the apparent equivalence of (+)-, (-)- and (+/-)-propranolol in rats for synergism with morphine.

Analgesics, Opioid↗