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Cyclic AMP‐dependent anion secretion in human small and large intestine
Author(s) -
BRZUSZCZAK IM,
ZHAO J.,
BELL C.,
STIEL D.,
FIELDING I.,
PERCY J.,
SMITH R.,
O'LOUGHLIN EV
Publication year - 1996
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1996.tb00084.x
Subject(s) - ibmx , bumetanide , secretion , cotransporter , dids , medicine , jejunum , endocrinology , chemistry , biology , biochemistry , forskolin , receptor , sodium , organic chemistry , membrane
Cyclic AMP‐dependent Cl secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP‐dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short‐circuit current (Isc) equivalent to the net increase in Cl secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl channel blocker), bumetanide (basolateral Na + /K + /2Cl cotransporter), BaCl 2 (basolateral K + channel) and Cl free buffer in both segments and indomethacin (cyclo‐oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo‐oxygenase in the colon. A small component of IBMX‐stimulated Isc was inhibited by acetazolamide. Cyclic AMP‐dependent secretion is largely apical Cl secretion, although a small component appears to be HCO 3 . Secretion is dependent on basolateral K + channels and Na + /K + /2Cl cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo‐oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.