Influence of "calcium2+-channel blockers" on exocrine pancreatic secretion by isolated rat acini.
Cytoplasmic Ca2+ is regarded as an intracellular messenger for acetylcholine- and cholecystokinin (CCK)-stimulated pancreatic enzyme secretion. We investigated in the in vitro model of isolated rat pancreatic acini whether or not Ca2+-channel blockers are able to inhibit Ca2+-mediated enzyme secretion. Isolated rat pancreatic acini were prepared via collagenase digestion. The effect of various Ca2+-channel blockers on amylase secretion stimulated by various secretagogues was monitored. Verapamil, but not nitrendipine, dose-dependently reduced CCK8- and carbachol-stimulated enzyme secretion. Higher doses of either CCK8 or carbachol could not reverse the inhibition caused by verapamil. Amylase secretion stimulated by the ionophore A23817 was not altered by verapamil. Verapamil augmented enzyme secretion stimulated by secretagogues which work through cAMP as second messenger. 3H-N-methylscopolamine- and 125I-Bolton-Hunter-CCK8-binding to pancreatic acini was dose-dependently inhibited by verapamil, but the inhibition curves did not parallel the inhibition curves with unlabeled receptor agonists. Thus, the impairment of exocrine pancreatic amylase secretion by verapamil is probably not due to its known "Ca2+-channel" blocking abilities in other tissues but is rather caused by noncompetitive effects on the level of muscarinic receptors and receptors for CCK.
Mössner
J
J
Medical Polyclinic, University of Würzburg, Federal Republic of Germany.
Schwarz
J
J
Fischbach
W
W
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D015290:Second Messenger Systems / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011949:Receptors, Cholecystokinin; D005711:Gallopamil; D002217:Carbachol; D009568:Nitrendipine; D000681:Amylases; D012844:Sincalide; D002118:Calcium