Cyclic adenosine-3',5'-monophosphate production is greater in rabbit duodenal crypt than in villus cells.
BACKGROUND
Duodenal surface epithelial cells secrete bicarbonate. Agonists of duodenal alkaline secretion (such as vasoactive intestinal polypeptide (VIP), prostaglandin E2 (PGE(2)), and forskolin) increase intracellular cyclic adenosine-3', 5-monophosphate (cAMP), and cAMP stimulates Cl-HCO(3)- exchange in duodenal brush border membrane vesicles. As intestinal villus and crypt cells differ in function, our aims were to contrast 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 degradation 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 crypt cells cAMP generation was approximately 10-fold greater (P < 0.001) in response to VIP, PGE(2), and forskolin than to villus cells. The relative 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.


CONCLUSIONS
cAMP production is greater in duodenal crypt than in villus enterocytes at rest and in response to forskolin, VIP, and PGE(2), suggesting that alkaline secretion may differ along the villus-to-crypt axis.
Amelsberg
M
M
Division of Gastroenterology, Dept. of Medicine, University of California at San Diego, California, USA.
Amelsberg
A
A
Ainsworth
M A
MA
Hogan
D L
DL
Isenberg
J I
JI
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001639:Bicarbonates; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D015232:Dinoprostone