In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 275, No. 6 ( 1998-12-01), p. G1274-G1281
Abstract:
Cl − secretion in the colon can be activated by an increase of either intracellular Ca 2+ or cAMP. In this study we examined a possible interdependence of the two second-messenger pathways in human colonic epithelium. When measured in a modified Ussing chamber, carbachol (CCH; 100 μmol/l, basolateral), via an increase in cytosolic Ca 2+ concentration ([Ca 2+ ] i ), activated a transient lumen-negative equivalent short-circuit current ( I sc ) [change (Δ) in I sc = −79.4 ± 7.5 μA/cm 2 ]. Previous studies indicated that intracellular Ca 2+ directly acts on basolateral K + channels, thus enhancing driving force for luminal Cl − exit. Increased intracellular cAMP (by basolateral addition of 100 μmol/l IBMX and 1 μmol/l forskolin) activated a sustained lumen-negative current (Δ I sc = −42.4 ± 7.2 μA/cm 2 ) that was inhibited by basolateral trans-6-cyano-4-( N-ethylsulfonyl- N-methylamino)-3-hydroxy-2,2-dimethyl & 2-chromane (10 μmol/l), a blocker of KvLQT1 channels. In the presence of elevated cAMP, the CCH-activated currents were augmented (Δ I sc = 167.7 ± 32.7 μA/cm 2 ), suggesting cooperativity of the Ca 2+ - and cAMP-mediated responses. Inhibition of endogenous cAMP production by indomethacin (10 μmol/l) significantly reduced CCH-activated currents and even reversed the polarity in 70% of the experiments. The transient lumen-positive I sc was probably due to activation of apical K + channels because it was blocked by luminal Ba 2+ (5 mmol/l) and tetraethylammonium (10 mmol/l). In the presence of indomethacin (10 μmol/l, basolateral), an increase of cAMP activated a sustained negative I sc . Under these conditions, CCH induced a large further increase in lumen-negative I sc (Δ I sc = −100.0 ± 21.0 μA/cm 2 ). We conclude that CCH acting via [Ca 2+ ] i can induce Cl − secretion only in the presence of cAMP, i.e., when luminal Cl − channels are already activated. The activation of a luminal and basolateral K + conductance by CCH may be essential for transepithelial KCl secretion in human colon.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.1998.275.6.G1274
Language:
English
Publisher:
American Physiological Society
Publication Date:
1998
detail.hit.zdb_id:
1477329-6
detail.hit.zdb_id:
603840-2
SSG:
12
