Interaction of physalaemin, substance P, and eledoisin with specific membrane receptors on pancreatic acinar cells.

Abstract

125I-labeled physalaemin was prepared and the kinetics, stoichiometry and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas were examined. Binding of 125I-labeled physalaemin was saturable, temperature-dependent and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 500 binding sites and binding of the tracer to these sites could be inhibited by physalaemin [concentration for half-maximal effect (Kd), 2 nM], substance P (Kd, 5 nM), or eledoisin (Kd, 300 nM) but not by cholecystokinin, caerulein, bombesin, litorin, gastrin, secretin, vasoactive intestinal peptide, glucagon, somatostatin, neurotensin, bovine pancreatic polypeptide, Leu-enkephalin, Met-enkephalin, atropine or carbamylcholine. With physalaemin, substance P and eledoisin, there was a close correlation between the relative potency for inhibition of binding of labeled physalaemin and that for stimulation of amylase secretion. For a given peptide, however, a 3-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, Ca outflux or cyclic GMP accumulation. Dispersed acini from guinea pig pancreas possess a single class of receptors that interact with physalaemin, substance P and eledoisin and occupation of 45% of these receptors will cause a maximal biological response.