Inhibitory responses to exogenous adenosine in murine proximal and distal colon

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Abstract
The aims of the present study were firstly, to characterize pharmacologically the subtypes of P1purinoreceptors involved in the inhibitory effects induced by exogenous adenosine in longitudinal smooth muscle of mouse colon, and secondly, to examine differences in the function and distribution of these receptors between proximal and distal colon. Adenosine (100 μM–3 mM) caused a concentration‐dependent reduction of the amplitude of spontaneous contractions in the proximal colon, and muscular relaxation in the distal colon. In the proximal colon, adenosine effects were antagonized by a selective A1receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX, 10 nM), but were not modified by 3,7‐dimethyl‐1‐propargylxanthine (DMPX, 10 μM) or by 9‐chloro‐2‐(2‐furanyl)‐5‐((phenylacetyl)amino)‐ [1,2,4]triazolo[1,5‐c]quinazoline (MRS 1220, 0.1 μM), selective A2and A3receptor antagonists, respectively. In the distal colon, adenosine effects were antagonized by DPCPX, DMPX, and by a selective A2Breceptor antagonist, 8‐[4‐[((4‐cyanophenyl)carbamoylmethyl)oxy]phenyl]‐1,3‐di(n‐propyl) xanthine (MRS 1754, 10 μM), but not by 8‐(3‐chlorostyryl)‐caffeine (CSC, 10 μM), a selective A2Areceptor antagonist, or by MRS 1220. Tetrodotoxin (TTX 1 μM), the nitric oxide (NO) synthase inhibitor,N‐nitro‐L‐arginine methyl ester (L‐NAME, 100 μM), or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (10 μM), an inhibitor of soluble guanylyl cyclase, reduced adenosine effects only in distal colon. In addition,L‐NAME induced a further reduction of adenosine relaxation in the presence of DPCPX, but not in the presence of MRS 1754. From these results we conclude that, in the murine proximal colon, adenosine induces inhibitory effectsviaTTX‐insensitive activation of A1receptor. In the distal colon, adenosine activates both A1and A2Breceptors, the latter located on enteric inhibitory neurons releasing NO. British Journal of Pharmacology(2006)148, 956–963. doi:10.1038/sj.bjp.0706808

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