EFFECT OF PLATELET-ACTIVATING-FACTOR AND ITS ANTAGONISTS ON COLONIC DYSMOTILITY AND TISSUE-LEVELS OF COLONIC NEUROPEPTIDES

We investigated whether platelet-activating factor (PAF) alters coloni c tissue levels of substance P and vasoactive intestinal peptide (VIP) , two neuropeptides that regulate colonic motility. Left colons were h arvested from NZ White Rabbits and underwent vascular perfusion via th e inferior mesenteric artery. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. Colons were perfused with either buffered saline alone or with 5.0 X 10(-5) M PAF. PAF administration increased tissue VIP and substance P levels a nd decreased the force of colonic contractions. Pretreatment with WEB- 2170 or alprazolam decreased concentrations of both tissue neuropeptid es, and decreased the force of colonic contractions and minute motilit y index. These results suggest that both VIP and substance P are stimu lated by PAF and may participate in colonic dysmotility during inflamm atory states.