Β-adrenergic Receptor Density Research Articles

Hippocampal α- and β-adrenergic receptors: comparison of [ 3H]dihydroalprenolol and [ 3H]WB 4101 binding with noradrenergic innervation in the rat

The relationship of α- and β-adrenergic receptors to the noradrenergic innervation of the rat hippocampal formation was studied with histofluorescent, biochemical, and radioligand binding methods. The dentate gyrus received a major portion of the innervation and contained twice the norepinephrine content of the hippocampal gyrus. However, the density of β-adrenergic receptors, determined by [ 3H]dihydroalprenolol (DHA) binding, was approximately equal in both gyri. By contrast, a presumed α-adrenergic binding site was relatively concentrated in the dentate gyrus, roughly correlating with the distribution of the noradrenergic innervation. Although a significant concentration of β-adrenergic receptors in the pyramidal cell layer had been suggested in previous studies with fluorescent analogs of propranolol, direct microchemical measurements of [ 3H]DHA binding in stratum pyramidalis and stratum radiatum showed that β-adrenergic receptors were uniformly distributed in the hippocampal gyrus. These data, demonstrating a ubiquitous distribution of β-adrenergic binding in a brain region with a well-defined noradrenergic input, suggest that a portion, perhaps a majority, of β-adrenergic receptors are not associated with noradrenergic nerve terminals.

Ontogeny of mammalian myocardial β-adrenergic receptors

Little information is available regarding the ontogenesis of the mammalian cardiac β-receptor and its relationship to physiological responses. In this study, β-adrenergic receptors were identified and characterized in the fetal, neonatal, and adult mouse heart using [3H]-(−)-dihydroalprenolol ([3H]-DHA). The fetal mouse heart (FMH) in organ culture was used to study the development of responsiveness to the β-agonist, (−)-isoproterenol. Whereas 13 day (d) fetal mouse hearts were insensitive to (−)-isoproterenol, hearts from 21 d fetal mouse responded to (−)-isoproterenol with an approximate doubling of the heart rate. The dissociation constant (KD) of [3H]-DHA for the β-adrenergic receptor (0.3 nM) remained unaltered during development. In contrast, β-adrenergic receptor density expressed as percentage of the adult receptor density was: 14% for 13 d FMH; 29% for 15 d FMH; 41% for 17 d FMH; 65% for 19 d FMH; 73% for 21 d FMH; 93% for 1 d neonate; 168% for 3 d neonate, and 173% for 14 d neonate. These data suggest that the β-adrenergic receptor, detected by [3H]-DHA binding, (1) appears prior to a detectable heart rate response, (2) has significant increases during the third trimester which parallel the increased adrenergic responsiveness, and (3) dramatically increases in the postnatal period before declining to the adult level.

Electroconvulsive shock treatment decreases β-adrenergic receptor sensitivity in rat brain

ELECTROCONVULSIVE SHOCK (ECS) is one of the most effective forms of therapy available for patients with depression1. Its mechanism of action, however, is not clear. Like other antidepressants, ECS probably augments the postsynaptic availability of neurotransmitters, for it increases the release and turnover of noradrenaline (NA)2–4, decreases NA uptake5, and raises the activity of tyrosine hydroxylase. Also, synthesis of cyclic AMP stimulated by NA (NA-sensitive adenylate cyclase) is reduced in brain tissues obtained after chronic treatment with ECS6,7. It has been reported that chronic administration of antidepressant drugs reduces β-adrenergic receptor density in the rat brain8. Because ECS is another form of treatment for depressive illness, we examined whether chronic administration of ECS has effects similar to those of other antidepressants on β-adrenergic receptor sensitivity in rat brain. We report here that we observed a significant decrease in β-adrenergic sensitivity following chronic ECS treatment. The relationship between such observed effects and clinical response requires further investigation.

Alpha- and beta-adrenergic receptors of the rat salivary gland elevation after chemical sympathectomy

Binding of [ 3H]dihydroergokryptine and [ 3H]dihydroalprenolol to membrane preparations from rat submaxillary gland was measured to characterize the α- and β-adrenergic receptors, respectively. Kinetic analysis of the data revealed a high affinity binding site for each radioligand. Inhibition of binding at each site was stereospecific for the active isomer of the catecholamine used. The greater ability of a β 1 and β 2 specific β-adrenergic antagonist to displace [ 3H]dihydroalprenolol binding indicated that this binding site was of teh β 1 type. Chemical sympathectomy with reserpine or 6-hydroxydopamine resulted in a significant increase in both [ 3H]dihydroalprenolol and [ 3H]dihydroergokryptine binding in the rat submaxillary gland. Scatchard analysis of the data indicated that these increases in binding were due to a change in total number of binding sites for [ 3H]dihydroergokryptine and [ 3H]dihydroalprenolol with little change in apparent affinities. This suggests that changes in α- and β-adrenergic receptor density may be important in the development of supersensitivity in salivary glands after reserpine and 6-hydroxydopamine treatment.

β-Adrenergic receptor density in brains of ethanoldependent rats

β-Adrenergic receptor density in brains of ethanoldependent rats

Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain

CHRONIC administration of either tricyclic antidepressant drugs or monoamine oxidase inhibitors, which are effective in the treatment of endogenous depression, has been shown to decrease the sensitivity of nor adrenaline (NA)-stimulated adenylate cyclase1–5 and to decrease the apparent density of β-adrenergic receptor binding sites in rat brain6–10. This alteration in receptor mechanisms by antidepressant drugs seems to be selective, as neither α-adrenergic nor serotonergic receptor binding in rat cortex is altered by the tricyclic drug desipramine7. It is therefore of interest to know whether other forms of antidepressant intervention alter receptor mechanisms in the brain and if so, whether they display a time course and selectivity similar to that of antidepressant drugs. Here, we have investigated the effects of a single and of multiple electroconvulsive shocks (ECS) on rat brain monoaminergic receptor binding sites and report that the density of β-adrenergic receptors is decreased.

β-adrenergic and muscarinic cholinergic receptors in rat submaxillary glands. Effects of thyroidectomy

Administration of triiodothyronine to thyroidectomized rats increased the density of β-adrenergic receptors in rat submaxillary gland without significantly changing the density of muscarinic cholinergic receptors. Thus, thyroid hormone appears to regulate β-adrenergic sensitivity in the rat salivary gland.

Topical epinephrine causes a decrease in density of β-adrenergic receptors and catecholamine-stimulated chloride transport in the rabbit cornea

A single administration, or twice daily administration for 4.5 days, of topical 2% epinephrine to the rabbit eye in vivo causes a 30–40% decrease in the density of β-adrenergic receptors on membranes prepared from the cornea. Such treatment also causes complete loss of the ability of excised corneas to respond to epinephrine in vitro with enhanced active chloride transport. These findings indicate that stimulation with a high concentration of catecholamine depresses the entire pathway from receptor to physiological response.

Chronic guanethidine treatment increases cardiac β-adrenergic receptors

VARIOUS pharmacologically active agonists capable of altering cell function have been shown to interact primarily with specific receptors on the outer cell membrane1. Evidence has accumulated from several systems to suggest that there may be a dynamic and inverse relationship between the number or density of receptors on the membrane surface and the degree of receptor occupancy by agonist2,3. We present here experiments which demonstrate in rat hearts that chronic withdrawal of adrenergic stimulation produced by guanethidine treatment in vivo results in increased cardiac β-adrenergic receptor density. Further, in isolated, perfused hearts obtained from guanethidine-treated animals, there is an increased cyclic AMP (cAMP) accumulation in response to the β-adrenergic agonist isoprenaline, suggesting that the increased numbers of receptors may be related to the increased biochemical response.

Characterization of α- and β-adrenergic receptors in membranes prepared from the rabbit iris before and after development of supersensitivity

α-Adrenergic and β-adrenergic receptors were studied by measuring the binding of [ 3H]dihydroergocryptine and [ 3H]dihydroalprenolol, respectively, to membranes prepared from homo-genized rabbit irides. The binding of [ 3H]dihydroergocryptine appears to be specific for α-adrenergic receptors as adrenergic agents displace this radioligand with the following order of potency: phentolamine > epinephrine ⩾ norepinephrine ⪢ isoproterenol = propranolol. The binding of [ 3H]dihydroalprenolol appears to be specific for β-adrenergic receptors as adrenergic agents displace this radioligand with the following order of potency: propranolol ⪢ isoproterenol ⩾ epinephrine > norepinephrine ⪢ phentolamine. Several weeks after removal of the superior cervical ganglion, when all the adrenergic nerves to the tissue have degenerated, membranes prepared from denervated irides have an increased density of β-adrenergic receptors with no increase in the density of α-adrenergic receptors. A small decrease in the total number of α-adrenergic receptors probably occurs, which is due to the loss of pre-junctional receptors. The affinities of the receptors do not change. These findings suggest that unlike skeletal muscle, the supersensitivity that occurs in smooth muscle is not due to an increase in the population of receptors governing contraction. However, the change in population of β-adrenergic receptors is consistent with the hypothesis that, as in other tissues, the level of cyclic AMP modulates the density of the β-adrenergic receptor.

Ouabain and sodium effects on chloride fluxes across the isolated bullfrog cornea.

Ouabain and sodium effects on chloride fluxes across the isolated bullfrog cornea.