Effects of Vasoactive Intestinal Peptide, Secretin, and Related Peptides on Rat Colonic Transport and Adenylate Cyclase Activity

Abstract

Vasoactive intestinal peptide (VIP), secretin, glucagon, gastric inhibitory peptide (GIP), and partial sequences of VIP and secretin were examined for their effect on colonic transport and adenylate cyclase activity. Net water flow was measured gravi- metrically in muscle-stripped, everted sacs of ascending and descending rat colon. VIP and secretin, but not glucagon or GIP, stimulated colonic secretion. The sensitivity of the colonic mucosa to VIP was high: the threshold (10–11 m ) and half-maximal dose (10–10 m ) for the effect of VIP were a 1000 times less than the threshold (10–8 m ) and half- maximal dose (10 –7 m ) for the effect of secretin. A subthreshold concentration of theophylline (2 mM) increased the submaximal responses to VIP or secretin up to but not beyond the maximal response to VIP alone (4.1 ± 0.2 μl mg-1 30 min-1). The combined effect of secretin and a maximal concentration of VIP was not additive. These results indicated that VIP and secretin shared the same receptor sites and/or intermediary mechanisms. VIP14–28 acted as a partial agonist with an efficacy of 0.2 and inhibited significantly the response to VIP. Secretin5–27 showed no secretory activity and did not inhibit the response to secretin. The lactamimide RMI 12330A (10-3 m ) abolished the secretory response to VIP and secretin but had no effect on the secretory response to 10 mM theophylline or on control absorptive flow rate. VIP and secretin, but not glucagon or GIP, stimulated adenylate cyclase activity in homogenates of colon mucosa. The lactamimide RMI 12330A (10-3 m ) inhibited basal adenylate cyclase activity as well as activity stimulated by VIP, secretin, prostaglandin E1, and 5'-guanylyl imidodiphosphate. The results obtained in colon mucosa conform to a pattern of structural and functional homology exhibited by VIP and secretin in several tissues (fat, liver, and pancreatic acinar cells) which sets them apart from glucagon and GIP. The mode of action of VIP and secretin on colonic secretion appears to involve the adenylate cyclasecyclic AMP system. The abundance of VIP in the colon of many species and the high sensitivity of transport mechanisms to VIP shown in this study raise the possibility that VIP may play a local (i.e., paracrine and/or neurocrine) role in the regulation of colonic transport.