ANP INHIBITS NACL ABSORPTION AND ELICITS CL SECRETION IN PORCINE COLON - EVIDENCE FOR CGMP AND CA MEDIATION

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 o f neutral Na and Cl absorption and elicited electrogenic Cl secretion. Amiloride, at a concentration that inhibits Na-H exchange, produced a n identical inhibition of Na transport and abolished the ANP-induced d ecrease in Na absorption. In contrast, serosal addition of bumetanide, an inhibitor of Na-K-2Cl cotransport, partially inhibited the short-c ircuit current (I(sc)) response to ANP. Whereas 8-bromoguanosine 3',5' -cyclic monophosphate (8-BrcGMP) produced qualitatively similar effect s 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 wi th ANP induced a threefold increase in cGMP content, whereas cAMP was unaffected. The ANP-induced Cl secretion and I(sc) were diminished wit h tetrodotoxin and verapamil, whereas these agents were without effect on the ANP-induced inhibition of Na and Cl absorption. Results indica te that ANP inhibits net colonic absorption of ions by antiabsorptive and secretory mechanisms that are dependent on both cGMP and Ca.