Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells.
Binding of 125I-labeled vasoactive intestinal peptide (VIP) to dispersed enterocytes prepared from guinea pig small intestine was saturable, temperature dependent, and reversible, and reflected interaction of the labeled peptide with a single class of binding sites. Each enterocyte possessed approximately 60,000 binding sites and binding of the tracer to these sites could be inhibited by VIP [concentration for half-maximal effect (Kd), 12 nM] and by secretin (Kd greater than 1 micro M), but not by glucagon, gastrin, cholecystokinin, calcitonin, bombesin, litorin, physalaemin, substance P, eledoisin, serotonin, carbamylcholine, or histamine. With VIP and secretin, there was a close correlation between the relative potency for inhibition of binding of 125I-VIP and that for increasing cellular cAMP. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of cellular cAMP. In addition to inhibiting binding of 125I-VIP and increasing cellular cAMP in enterocytes, secretin caused an increase in short-circuit current across guinea pig small intestine in vitro. Prostaglandin E1 increased cellular cAMP, but did not alter binding of 125I-VIP and the increase in cAMP caused by prostaglandin E1 plus VIP or secretin was equal to the sum of the increase caused by each agent alone.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012633:Secretin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D005755:Gastrins; D005768:Gastrointestinal Hormones; D011956:Receptors, Cell Surface; D012633:Secretin; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D002217:Carbachol; D005934:Glucagon; D002766:Cholecystokinin; D000242:Cyclic AMP