Modification by islet-activating protein of receptor-mediated regulation of cyclic AMP accumulation in isolated rat heart cells.
Free cells isolated from adult rat heart by the collagenase method were maintained in culture up to 21 h with or without an islet-activating protein (IAP) that had been purified from the culture medium of Bordetella pertussis. Short-term stimulation of beta-adrenergic or glucagon receptors in these cultured cells caused more accumulation of cAMP in cells precultured with IAP (IAP-treated) than in nontreated cells, although there was no significant difference in the baseline (non-stimulated) content of cAMP between these cells. Stimulation of muscarinic cholinergic or adenosine R-site receptors caused a marked inhibition of cAMP accumulation in nontreated cells in either the presence or absence of a beta-agonist (or glucagon); no such inhibition was essentially observed in IAP-treated cells. These actions of IAP developed gradually and were dose-dependent with the half-maximal concentration of approximately 80 ng/ml in culture. It is concluded that IAP may exert its unique influence on the heart cell membrane causing profound modification of the coupling mechanism involved in the receptor-mediated activation or inhibition of adenylate cyclase. This action of IAP differs clearly from that of cholera toxin which activates adenylate cyclase rather independently of the receptor functions in heart cells.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004793:Enzyme Reactivators / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D011953:Receptors, Cyclic AMP
D004793:Enzyme Reactivators; D011453:Prostaglandins; D011953:Receptors, Cyclic AMP; D005934:Glucagon; D000242:Cyclic AMP; D007545:Isoproterenol; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine