title: Irreversible photoactivation of a pancreatic secretagogue receptor with cholecystokinin COOH-terminal octapeptides.
abstract: The photochemically reactive analog of cholecystokinin octapeptide (CCK-8), 2-nitro-5-azidobenzoyl-Gly-Asp-Tyr-(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2 (NAB-Gly-CCK-8), has been used to stimulate irreversibly the receptor for CCK-8 on preparations of dispersed guinea pig pancreatic acini. When continuously present with acini in the dark, NAB-Gly-CCK-8 is a reversible stimulant of secretory protein discharge with an ED50 of 0.4 nM. After six cycles of photolysis of acini with NAB-Gly-CCK-8 followed by extensive washing and assay in peptide-free medium in the dark, the photoactivated label induces irreversible discharge. Irreversible discharge is proportional to the concentration of NAB-Gly-CCK-8 present during photolysis and is nearly equivalent in intrinsic activity to that induced by CCK-8 in the dark. Inclusion of a 5-fold excess of prephotolyzed NAB-Gly-CCK-8 during photolysis partially protects against irreversible discharge, suggesting that the receptor irreversibly stimulated by NAB-Gly-CCK-8 is likely a receptor for peptides in the CCK family. Irreversible discharge requires metabolic energy supplied by oxidative phosphorylation and is dependent on extracellular Ca2+ and, thus, resembles that induced by reversible secretagogues.
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010777:Photochemistry; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide
chemical_list: D011956:Receptors, Cell Surface; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002766:Cholecystokinin; D012844:Sincalide; D002118:Calcium