Blockade of heterologous desensitization of prostate adenylate cyclase without blockade of homologous down regulation of receptors or loss of GTP regulation of agonist binding.
Exposure of rat prostatic tissues to isoproterenol resulted in rapid desensitization of their catecholamine-sensitive adenylate cyclase which was associated with reduction of available beta-adrenoceptors and a loss of guanine nucleotide-mediated regulation of agonist binding to these receptors. The effect of isoproterenol treatment on responsiveness of the adenylate cyclase was prevented by acetylcholine, high potassium ion, or the calcium ionophore A23187. Preservation of responsiveness was not accompanied by maintenance of available beta-adrenoceptors or maintenance of guanine nucleotide regulation of agonist bindings. These results suggest that the lesion of the guanine nucleotide regulating components coupled to the catalytic moiety of the enzyme complex is a crucial factor in the desensitization of catecholamine-sensitive adenylate cyclase and the preservation of enzyme reaction could be accomplished by agents increasing intracellular calcium, which in turn, maintain the nucleotide regulatory components coupling to the cyclase in a protective environment from desensitization.
D000109:Acetylcholine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000001:Calcimycin; D004082:Dihydroalprenolol; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D000109:Acetylcholine; D011188:Potassium