title: Ketotifen increases cyclic adenosine 3',5'-monophosphate in intact human lymphocyte and potentiates other adenylate cyclase activating agents.
abstract: We have investigated the effects of ketotifen on the cyclic adenosine 3',5'-monophosphate (cyclic AMP) response of intact human lymphocyte and its interaction with adenylate cyclase activating agents. In the presence of cyclic AMP phosphodiesterase inhibitor (3-isobutyl-1-methyl-xanthine), ketotifen (10(-8)-10(-4) M) caused an 80% increase in cyclic AMP content of human lymphocyte, a magnitude similar to that observed with hydrocortisone. The cyclic AMP level peaked at about 15 minutes and remained elevated for at least 45 minutes. In addition, ketotifen (10(-6)-10(-4) M) markedly potentiated the effect of several adenylate cyclase stimulating agents, including L-isoproterenol, prostaglandin E1 and forskolin. The biochemical mechanisms underlying these effects are unknown. It may be at least partly related to the ability of ketotifen to reverse and prevent beta 2 adrenoceptor desensitization and to promote the formation of hormone - nucleotide - high affinity receptor complex. These effects may contribute to its prophylactic effect in the treatment of bronchial asthma.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D004357:Drug Synergism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology*; D008214:Lymphocytes / Q000032:analysis / Q000187:drug effects*
chemical_list: D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000527:Alprostadil; D007545:Isoproterenol; D006854:Hydrocortisone; D007665:Ketotifen