Cyclooxygenase inhibitors affect Met-enkephalin- and acetylcholine-stimulated motility of the isolated rat colon.

Endogenous prostaglandins have been shown to modify the contractile activity of the intestinal muscle. In this study, the effects of the cyclooxygenase inhibitors phenylbutazone, diclofenac, indomethacin, acetylsalicyclic acid (ASA) and salicyclic acid (SA) on the motility of the Met-enkephalin- (FK) and acetylcholine- (ACh) stimulated isolated rat colon were observed. Intraluminal pressure changes were measured by perfusion manometry in organ preparations maintained in a standard organ bath. FK and ACh dose-dependently increased intraluminal tonic pressure with a response of 42 +/- 0.6 arbitrary units (mean +/- S.E., n = 6) at 10(-6) M FK and of 96.8 +/- 8.6 arbitrary units at 10(-4) M ACh. Oral pretreatment with ASA (300 mg/kg b.i.d. for 3 days and 1 h before removal of the colon) suppressed the stimulatory effect of FK and significantly reduced ACh stimulation of colonic tone. A similar effect was observed when ASA alone was added to the nutrient. Phenylbutazone, diclofenac or indomethacin (10(-4)-10(-3) M) in the nutrient also significantly inhibited the effects of both stimulants. In contrast, p.o. pretreatment with SA (100 mg/kg b.i.d. for 3 days and 1 h before removal of the colon) did not affect stimulatory properties of FK and ACh. SA given with the nutrient exerted a substantial inhibition of the stimulated tone. One-hour washout was sufficient to completely abolish the inhibitory action of SA but reduced that of ASA by only 25%. The data suggest that endogenous prostaglandins and/or thromboxanes are involved in the FK- and ACh-stimulated contraction of rat colonic smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)