title: Effects of calcium channel blockers and ketotifen on beta 2 adrenergic receptor regulation in intact human lymphocytes.
abstract: Effects of three calcium channel blockers (nifedipine, NIF; verapamil, VER and diltiazem, DIL) and one antiallergic drug, ketotifen (KET) on isoproterenol (ISO)-induced beta 2 adrenergic receptor desensitization and resensitization have been studied with intact human lymphocytes in vitro. While incubation of lymphocytes with 1.0 microM NIF, VER, or DIL alone neither changed [3H]-CGP-12177 binding (Bmax) nor increased cAMP responsiveness to ISO, they all partially prevented 50 nM ISO-induced beta 2 adrenoceptor-adenylate cyclase uncoupling. VER and DIL also partially prevented beta 2 adrenoceptor down-regulation, but NIF did not. In contrast, 10 microM KET not only diminished ISO-induced desensitization but also accelerated subsequent resensitization. KET alone also induced an up-regulation of cell surface beta adrenergic receptors. The effects of these compounds on beta 2 adrenoceptor regulation may partially explain their potentiation of ISO-induced cAMP accumulation in lymphocytes.
authors.affiliation: Department of Medicine, UCLA School of Medicine, 90024.
authors.forename: K K
authors.initials: KK
authors.lastname: Hui
authors.forename: J L
authors.initials: JL
authors.lastname: Yu
mesh_terms: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol; D007665:Ketotifen / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D007545:Isoproterenol; C033394:CGP 12177; D007665:Ketotifen