Metalloendopeptidase inhibitors and stimulus-secretion coupling in the mouse exocrine pancreas.
Inhibitors of metalloendopeptidases interfere with events involving Ca2(+)-dependent membrane fusion in a number of cell types. The divalent ion chelating agent 1,10-phenanthroline inhibited pancreatic amylase secretion stimulated by carbachol, cholecystokinin-octapeptide (CCK-8), or bombesin, but detailed studies indicated that this is unlikely to be a result of inhibition of metalloendopeptidase activity. The binding of [3H]N-methylscopolamine to pancreatic acini was reduced by 1,10-phenanthroline and this would explain the marked inhibition of carbachol-induced amylase secretion by the chelating agent. CCK-8-stimulated hydrolysis of phosphatidylinositol-4,5-bisphosphate was reduced by 1,10-phenanthroline while the binding of CCK-8 to acini was not affected. This inhibition of hydrolysis would explain the inhibition of CCK-8- and bombesin-induced amylase secretion. The metalloendopeptidase substrate carbobenzoxyglycylphenylalanylamide did not affect bombesin-stimulated amylase secretion. Amylase secretion evoked by treating pancreatic acini with the ionophore A23187 or dibutyryl-cyclic AMP was not reduced by 1,10-phenanthroline, indicating a lack of involvement of metalloendopeptidases in the process of exocytosis in this cell type.
Department of Physiology, University of Adelaide, South Australia.
S P
SP
Collins
M L
ML
Roberts
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D019832:N-Methylscopolamine; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010618:Phenanthrolines / Q000494:pharmacology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology
D004151:Dipeptides; D010618:Phenanthrolines; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D000001:Calcimycin; C066375:carbobenzoxyglycylphenylalanine amide; D003994:Bucladesine; D002217:Carbachol; D000681:Amylases; D008666:Metalloendopeptidases; D012844:Sincalide; D001839:Bombesin; D019832:N-Methylscopolamine; C025205:1,10-phenanthroline