DISTENSION-INDUCED ELECTROGENIC CL- SECRETION IS MEDIATED VIA VIP-ERGIC NEURONS IN RAT RECTAL COLON

Distension of rat rectal colon causes electrogenic Cl- secretion via t he plexus submucosus Meissner. This study aimed to identify the neurot ransmitter(s) of this reflex pathway. Distension was applied to partia lly stripped rat rectal colon in Ussing chambers. Baseline short-circu it current (I-sc) increased and then slowly declined again within 30 m in. The increase in I-sc 10 min after distension (Delta I-sc(10)) was 1.8 +/- 0.3 mu mol . h(-1). cm(-2). Atropine (1 mu M) did not alter De lta I-sc(10). Thus cholinergic neurons with muscarinic synapses were n ot involved. Tissues were then desensitized to vasoactive intestinal p eptide (VIP) or substance P. This required continuous infusion of VIP or substance P into the chamber; otherwise, desensitization was only t emporary due to rapid degradation of VIP or substance P. During substa nce P desensitization, distension still induced a secretory response ( Delta I-sc(10) not significant vs. control), whereas during VIP desens itization distension no longer had an effect. Furthermore, a polyclona l anti-VIP antiserum blocked 81% and the VIP antagonist [p-Cl-D-Phe(6) ,Leu(17)]VIP blocked 89% of the distension-induced Delta I-sc(10), sup porting the results of the desensitization experiments. To localize th e site of VIP action, tetrodotoxin (TTX) was used. The TTX effect on I -sc during VIP stimulation was not different from its effect on baseli ne I-sc. This is in accord with the concept that the VIP receptors are mainly located on the enterocytes. We conclude that VIP, but not subs tance P or acetylcholine (via muscarinic receptors), acts as a neurotr ansmitter in the distension-induced reflex pathway, causing Cl- secret ion in rat rectal colon.