ANP inhibits NaCl absorption and elicits Cl secretion in porcine colon: evidence for cGMP and Ca mediation

R. A. Argenzio and M. Armstrong Department of Anatomy, North Carolina State University, College of Veterinary Medicine, Raleigh 27606. The effects of atrial natriuretic peptide (ANP) on ion transport were examined in the isolated, short-circuited proximal colon epithelium of the pig. Addition of ANP to the serosal solution decreased the rate of neutral Na and Cl absorption and elicited electrogenic Cl secretion. Amiloride, at a concentration that inhibits Na-H exchange, produced an identical inhibition of Na transport and abolished the ANP-induced decrease in Na absorption. In contrast, serosal addition of bumetanide, an inhibitor of Na-K-2Cl cotransport, partially inhibited the short-circuit current (Isc) response to ANP. Whereas 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) produced qualitatively similar effects as ANP, relatively high concentrations of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or prostaglandin E2 were required to alter NaCl transport. Furthermore, incubation of colonic mucosa with ANP induced a threefold increase in cGMP content, whereas cAMP was unaffected. The ANP-induced Cl secretion and Isc were diminished with tetrodotoxin and verapamil, whereas these agents were without effect on the ANP-induced inhibition of Na and Cl absorption. Results indicate that ANP inhibits net colonic absorption of ions by antiabsorptive and secretory mechanisms that are dependent on both cGMP and Ca.