title: Phenylarsine oxide inhibits agonist-induced changes in photolabeling but not agonist-induced desensitization of the beta-adrenergic receptor.
abstract: In the human lymphocyte, desensitization of the beta-adrenergic receptor-adenylate cyclase complex is associated with sequestration of the receptor as well as a change in photolabeling of beta-receptor proteins. Thus, desensitization of the lymphocyte beta-adrenergic receptor-adenylate cyclase system is associated with a selective reduction in the photoaffinity labeling of an Mr approximately equal to 55,000 beta-adrenergic receptor-binding site as compared to an Mr approximately equal to 68,000 beta-adrenergic receptor-binding moiety. In order to examine the relationship between sequestration and reduction in labeling of the Mr approximately equal to 55,000 peptide, we have studied the effect of phenylarsine oxide (an inhibitor of beta-receptor sequestration in astrocytoma cells) on agonist-induced desensitization of the beta-adrenergic receptor-adenylate cyclase system in circulating lymphocytes. Incubation of cells with phenylarsine oxide prior to exposure to agonists did not block the consequent reduction in isoproterenol-stimulated adenylate cyclase activity. However, sequestration of the receptor, as assessed by a decrease in accessibility of beta-adrenergic receptors on intact cells to hydrophilic receptor ligands, is blocked by phenylarsine oxide. Thus, the agonist-induced reduction in binding of the hydrophilic beta-adrenergic receptor ligand CGP-12177 was blocked by phenylarsine oxide (without phenylarsine oxide, 57 +/- 6% of control, with phenylarsine oxide, 97 +/- 3% of control). Photolabeling studies with [125I]iodocyanopindolol diazirine revealed that phenylarsine oxide pretreatment also blocked the selective loss in labeling of the Mr approximately equal to 55,000 beta-adrenergic receptor protein. These data suggest that agonist-induced alterations in the photolabeling pattern of the lymphocyte beta-adrenergic receptor that occur with desensitization closely parallel the apparent sequestration of beta-adrenergic receptors but can be dissociated from the initial desensitization phenomenon.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D000345:Affinity Labels / Q000378:metabolism; D001152:Arsenicals / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
chemical_list: D000318:Adrenergic beta-Agonists; D000345:Affinity Labels; D001152:Arsenicals; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C029341:oxophenylarsine; D000262:Adenylyl Cyclases; C033394:CGP 12177; D004229:Dithiothreitol