RECTAL DISTENSION-INDUCED COLONIC NET WATER SECRETION IN RATS INVOLVES TACHYKININS, CAPSAICIN SENSORY, AND VAGUS NERVES

Background & Aims: Distention of the intestine induces neural anion se cretion in vitro. Both substance P and neurokinin A modify water and i on transport in vivo. This study investigated in vivo (1) the effect o f rectal distention (RD) on proximal colonic net water flux, (2) the r ole of tachykinins, and muscarinic and nicotinic connections, and (3) the influence of capsaicin-sensitive nerves and vagotomy in this effec t. Methods: In anesthetized rats, colonic loops were infused with [C-1 4]poryethylene glycol 4000 Ringer's buffer. Net water flux was calcula ted according to C-14 activity in the effluent collected. RD was perfo rmed by inflation of a balloon (2 mL) in the rectum. Results: RD induc ed a colonic net water hypersecretion. This effect was blocked by prev ious systemic capsaicin, vagotomy, atropine, and hexamethonium treatme nt. Both neurokinin 1 (NK1) (SR-140,333; 1 mg/kg) and NK2 (MEN-10,621; 150 mu g/kg) antagonists administered intraperitoneally suppressed th e RD-hypersecretory effect, whereas NK2 (MEN-10,627; 1.5 mu g/kg) and NK3 (SR-142,801; 0.01 mg/kg) antagonists are active when injected intr acerebroventricularly. Conclusions: In vivo RD induces colonic net wat er secretion in rats, involving capsaicin-sensitive innervation and va gal nerves. This effect involves tachykininergic pathways at both peri pheral and central levels.