CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE PRODUCTION IS GREATER IN RABBIT DUODENAL CRYPT THAN IN VILLUS CELLS

Duodenal surface epithelial cells secrete bicarbonate. Agonists of duo denal alkaline secretion (such as vasoactive intestinal polypeptide (V IP), prostaglandin E(2) (PGE(2)), and forskolin) increase intracellula r cyclic adenosine-3',5'-monophosphate (cAMP), and cAMP stimulates Cl- HCO3- exchange in duodenal brush border membrane vesicles. As intestin al villus and crypt cells differ in function, our aims were to contras t cAMP generation in duodenal villus versus crypt cells in response to VIP, PGE(2), and forskolin. Methods: Villus and crypt rabbit duodenal enterocytes were isolated by calcium chelation. To prevent the degrad ation of cAMP in vitro, phosphodiesterase activity was inhibited. cAMP production was quantitated in response to VIP (10(-10)-10-(5)M), PGE( 2) (10(-10)-10(-4)M), and forskolin (10(-8)-10(-3)M). Results: In cryp t cells cAMP generation was approximately 10-fold greater (P < 0.001) in response to VIP, PGE(2), and forskolin than to villus cells. The re lative orders of potency (that is, D-50, VIP > PGE(2) > forskolin) and efficacy (that is, V-max, forskolin > VIP and PGE(2)) were similar in villus and crypt cells. Conclusion: cAMP production is greater in duo denal crypt than in villus enterocytes at rest and in response to fors kolin, VIP, and PGE(2), suggesting that alkaline secretion may differ along the villus-to-crypt axis.