Effects of proglumide on pancreatic acinar cell function.
Proglumide, a putative gastrin receptor antagonist, inhibited cholecystokinin (CCK)-stimulated amylase release and [3H]-2-deoxy-D-glucose uptake by isolated mouse pancreatic acini. Inhibition was reversible and competitive in nature with a KI of 0.7 mM. Proglumide also competitively inhibited the binding of 125I-CCK to its receptor in pancreas and brain; the KI for this interaction was 1.0 mM. In contrast, proglumide did not inhibit carbachol-stimulated amylase release, insulin-stimulated glucose transport and protein synthesis, or the binding of insulin to its receptors. Proglumide at 10 mM did, however, reduce both basal [3H]-2-deoxy-D-glucose uptake and [3H]-leucine incorporation into protein. We conclude that proglumide is a competitive and specific, albeit weak antagonist of CCK receptors. Higher concentrations of the drug may have other more nonspecific effects.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D011377:Proglumide / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects; D011949:Receptors, Cholecystokinin
D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D005973:Glutamine; D002766:Cholecystokinin; D003847:Deoxyglucose; D011972:Receptor, Insulin; D000681:Amylases; D011377:Proglumide