INVERSE REGULATION OF ALPHA-ADRENOCEPTOR AND BETA-ADRENOCEPTOR DURING TRINITROBENZENESULFONIC ACID (TNB)-INDUCED INFLAMMATION IN GUINEA-PIG SMALL-INTESTINE

The hypothesis has been raised that intestinal motor disturbances induced by inflammation of the digestive tract may reflect alterations in intestinal cell-membrane receptors. This question has been addressed herein for adrenoceptors by performing [H-3]prazosin, [H-3]rauwolscine and [H-3]DHA binding studies on guinea-pig jejunal smooth-muscle membrane preparations from both healthy controls and 3, 6, and 10 days after TNB-induced intestinal inflammation. Each of the adrenoceptor subtype-selective radioligands used bound selectively to a single saturable class of sites, with no significant (p<0.05) variation of dissociation constant (K(D)) values along the inflammatory process. In contrast maximal binding capacities (Bmax) for the different radioligands varied moderately but significantly (p<0.05 and p<0.01) according to the time after TNB injection. The a-adrenoceptors were significantly up-regulated, respectively from (mean +/- SE in fmoles/mg of proteins) 27 +/- 3.8 (controls) to 91 +/- 3.1 (day 10) for the alpha1-subtype, and from 26 +/- 2.7 (controls) to 102 +/- 5.9 (day 10) for the alpha2-subtype, In contrast beta-adrenoceptors were down-regulated from 384 +/- 34.6 (controls) to 158 +/- 17.2 (day 10). These findings highlighted an apparently inverse pathological regulation of intestinal alpha- and beta- adrenoceptor densities. They suggest that changes in intestinal adrenoceptors, probably resulting from functional denervation of the inflamed bowel tissue, may contribute to the altered intestinal motility observed in inflammatory bowel diseases.