Effects of calcium channel blockers and ketotifen on beta 2 adrenergic receptor regulation in intact human lymphocytes.

: 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.