Korean J Physiol Pharmacol.  1998 Aug;2(4):521-527.

cAMP-dependent signalling is involved in adenosine-stimulated Cl- secretion in rabbit colon mucosa

• Oh SO
• Kim EY
• Jung JS
• Woo JS
• Kim YK
• Lee SH

Abstract

An important property of the intestine is the ability to secrete fluid. The intestinal secretion is regulated by a number of substances including vasoactive intestinal peptide (VIP), ATP and different inflammatory mediators. One of the most important secretagogues is adenosine during inflammation. However, the controversy concerning the underlying mechanism of adenosine-stimulated Cl- secretion in intestinal epithelial cells still continues. To investigate the effect of adenosine on Cl- secretion and its underlying mechanism in the rabbit colon mucosa, we measured short circuit current (ISC) under automatic voltage clamp with DVC-1000 in a modified Ussing chamber. Adenosine, when added to the basolateral side of the mucosa, increased ISC in a dose-dependent manner. The adenosine-stimulated ISC response was abolished when Cl- in the bath solution was replaced completely with gluconate. In addition, the ISC response was inhibited by a basolateral Na-K-Cl cotransporter blocker, bumetanide, and by apical Clchannel blockers, dephenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenyl-propylamino)-benzoate (NPPB), glibenclamide. Amiloride, an epithelial Na+ channel blocker, and 4,4-diisothiocyanato-stilbene-2,2-disulphonate (DIDS), a Ca2+-activated Cl- channel blocker, had no effect. In the mucosa pre-stimulated with forskolin, adenosine did not show any additive effect, whereas carbachol resulted in a synergistic potentiation of the ISC response. The adenosine response was inhibited by 10 micrometer H-89, an inhibitor of protein kinase A. These results suggest that the adenosine-stimulated ISC response is mediated by basolateral to apical Cl- secretion through a cAMP-dependent Cl- channel. The rank order of potencies of adenosine receptor agonists was 5'-(N-ethylcarboxamino)adenosine(NECA) > N6-(R-phenylisopropyl)adenosine(R-PIA)>2-(p-(2-carbonylethyl)-phenyl-et hylamino)-5'-N-ethylcarboxaminoadenosine(CGS21680). From the above
results
, it can be concluded that adenosine interacts with the A2b adenosine receptor in the rabbit colon mucosa and a cAMP-dependent signalling mechanism underlies the stimulation of Cl- secretion.

Keyword

Adenosine; CAMP; Rabbit colon mucosa

MeSH Terms

Adenosine
Adenosine Triphosphate
Amiloride
Baths
Bumetanide
Carbachol
Colforsin
Colon*
Cyclic AMP-Dependent Protein Kinases
Epithelial Cells
Glyburide
Inflammation
Intestinal Secretions
Intestines
Mucous Membrane*
Purinergic P1 Receptor Agonists
Receptors, Purinergic P1
Vasoactive Intestinal Peptide
Adenosine
Adenosine Triphosphate
Amiloride
Bumetanide
Carbachol
Colforsin
Cyclic AMP-Dependent Protein Kinases
Glyburide
Purinergic P1 Receptor Agonists
Receptors, Purinergic P1
Vasoactive Intestinal Peptide