1,721,070 research outputs found
Advances on beta-adrenergic receptors. Molecular structure and functional regulation.
No full textThe diverse effects of the catecholamines (CA), epinephrine and norepinephrine, are mediated by a family of specific receptors (adrenergic receptors, AR). The beta-AR is a glycoprotein present in the membrane of a number of cell types. This receptor is closely associated with at least two other proteins, guanine nucleotide stimulating protein (Gs) and adenylate cyclase enzyme (AC), to form the beta-AR complex. The beta-AR recognizes the CA and is coupled to Gs which stimulates the effector enzyme AC. This enzyme converts ATP to cAMP and is the effector of the beta-AR complex. Thus the beta-AR is a G-coupled receptor which acts by raising intracellular levels of cAMP. The beta-AR is an important site of regulatory modifications through a variety of mechanisms. The best characterized is known as homologous desensitization: when the receptor is exposed to repeated stimuli by the agonist (CA), its responsiveness wanes, probably to compensate this potentially dangerous overstimulation. The gene for mammalian beta 2-AR has recently been cloned and the predicted amino acid sequence now opens the field to identification of the protein structures involved in receptor functions. The beta 2-AR protein is characterized by the presence of seven membrane spanning regions. The study of the structure, function and regulation of the beta-AR will extend our knowledge of the role of beta-AR in pathological conditions and suggest new therapeutic approaches
Glucocorticoids increase beta-adrenoceptors on human intact lymphocytes in vitro.
No full textA modification of beta-adrenoceptor binding has been observed in different human and animal tissues after glucocorticoid administration. In this study we observed that hydrocortisone increased human intact lymphocyte beta-adrenoceptors labelled with 3H-dyhydroalprenolol in vitro, in physiological and pharmacological concentrations. In saturation experiments hydrocortisone (10(-6)M) significantly raised beta-adrenoceptor Bmax and KD. Intact living lymphocytes seem to be a useful model for further investigation in man of the regulation of beta-adrenoceptors by glucocorticoids in physiological conditions
Selective reduction of one class of dopamine receptor binding sites in the corpus striatum of aged rats.
No full textIn aged rats (21-23 vs 3 month) the neuroleptic receptor number was reduced in the striatum (--53%), in the limbic area (--36%), and not changed in the cortex. The in vitro pharmacological profile of the remaining [3H]spiroperidol receptors in each area was not modified in aged animals. The binding of [3H]ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene) in the striatum and of [3H]serotonin ([3H]-5 HT) in the cortex was also the same in both age groups
Sulfinpyrazone increases the number of beta-adrenoceptors on intact human lymphocytes.
No full textSulfinpyrazone increased the number of beta-adrenoceptors (+ 17-40%) on intact human lymphocytes at concentrations ranging from 10(-5) to 2 X 10(-4) M. It affected the Bmax (187 +/- 6 and 142 +/- 5 fmol mg-1 protein respectively with and without sulfinpyrazone, P less than 0.001) but did not influence KD (4.4 +/- 0.3 and 4.6 +/- 0.7 nM with and without the drug). This effect was observed on either washed or unwashed lymphocyte membrane preparations. These findings have several pharmacological and therapeutic implications
The affinity of metergoline for 3H-Serotonin (5HT) binding sites is regulated by guanine nucleotide
No full text100 μM guanine nucleotide Gpp (NH)p reduces the affinity of the serotonergic antagonist metergoline for 3H-5HT binding sites in rat cerebral cortex. This effect is present both in inhibition binding and in saturation experiments. The hypothesis that the interaction of some serotonergic antagonists with 3H-5HT binding sites is regulated by guanine nucleotides is discussed. © 1983
Certain beta-blockers can decrease beta-adrenergic receptor number: I. Acute reduction in receptor number by tertatolol and bopindolol.
No full textWe have previously reported that a potent new beta-blocker, tertatolol, when given at therapeutic doses to healthy volunteers, rapidly reduced the number of human mononuclear leukocyte beta-receptors. In the present study, the mechanism of receptor regulation by beta-antagonists incubated with target cells in vitro was investigated. Two different cell types (human mononuclear leukocytes and S49 murine lymphoma cells) were used, and beta-adrenergic receptors were measured using either the hydrophilic ligand 3H-CGP 12177 (specific for surface receptors) or lipophilic 125I-pindolol (which measures total receptors). In a comparison between beta-blockers, tertatolol and bopindolol, but not propranolol and pindolol, were found to rapidly (1 hour at 37 degrees C) reduce the number of beta-adrenergic receptors. This was paralleled by a reduction in isoproterenol-stimulated cyclic AMP accumulation. The reduction in receptors was the same whether surface or total receptors were measured; thus, it was not due to receptor sequestration. This effect was not caused by partial agonist activity (bopindolol is a weak partial agonist); in parallel experiments, tertatolol and bopindolol, but not pindolol (potent partial agonist) and isoproterenol (full agonist), reduced beta-adrenergic receptors. Finally, this effect was not due to irreversible binding: the receptor reduction induced by the irreversible blocker bromo-acetyl-alprenolol-methane (BAAM) was stable for several hours, while the effect of tertatolol and bopindolol was slowly reversed over the same time course. We suggest that tertatolol and bopindolol have two effects on beta-adrenergic receptors: they bind competitively, and then they modify the receptors so that they are no longer available for binding by ligands or catecholamines
Molecular mechanisms that desensitize metabotropic glutamate receptor signaling: An overview
No full textThe purpose of the present article is to review our actual knowledge on the desensitization of metabotropic glutamate receptors based on the literature available so far, with the attempt to emphasize all converging data and to give a possible explanation to those evidences that still remain controversial. 1. We review our knowledge on the regulation of mGlu receptors based on the available literature 2. We report converging data and we comment on issues that still remain controversial. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. (c) 2012 Elsevier Ltd. All rights reserved.he purpose of the present article is to review our actual knowledge on the desensitization of metabotropic glutamate receptors based on the literature available so far, with the attempt to emphasize all converging data and to give a possible explanation to those evidences that still remain controversial. 1. We review our knowledge on the regulation of mGlu receptors based on the available literature 2. We report converging data and we comment on issues that still remain controversial. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'
Selective changes of receptor binding in brain regions of aged rats
No full textBinding to several receptors was compared in brain regions of 3 and 21-23 month-old rats. In crude membrane preparations of aged rats the number of dopamine antagonist receptors in striatum was much reduced (-53%). β-noradrenergic receptors (cortex) and benzodiazepine receptors (hippocampus and cerebellum) were less but significantly reduced and serotonergic receptors, α1 noradrenergic receptors (both in cortex) and dopamine agonist receptors (striatum) were unchanged. For each receptor binding the K(D) values were the same in young and old animals. GABA receptor binding (hippocampus and cerebellum) evaluated at only one 3H-GABA concentration (8 nM) was similar in both groups when expressed per protein content but significantly reduced in aged rats when expressed per tissue wet weight because of the partial purification of the synaptic membranes used for 3H-GABA binding. In our experimental conditions age-related changes of specific binding sites in the central nervous system were selective for some receptors studied and did not seem to be due to general non-specific modification of brain tissue composition
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