Evidence that prostaglandins are local regulatory agents in canine ileal circular muscle.
Studies were performed to determine the role of endogenous prostaglandins (PG) in regulating mechanical and electrical activities of canine ileal circular muscles. Indomethacin, a prostaglandin synthesis blocker, enhanced the amplitude of spontaneous and acetylcholine-stimulated contractions. The increase in mechanical activity caused by indomethacin was accompanied by decreased release of 6-keto-PGF1 alpha, the spontaneous metabolite of prostacyclin, from the muscle. The electrical mechanisms responsible for the changes in mechanical activity caused by indomethacin were investigated by intracellular measurement of electrical activity. The enhanced contractions due to indomethacin correlated with enhanced electrical slow-wave amplitude and generation of action potentials. After indomethacin treatment muscles were exposed to several exogenous prostaglandins to determine which of these compounds might reverse the mechanical effects of indomethacin. Prostacyclin reversed the effects of indomethacin, and PGE2 reversed some of the effects of indomethacin. Prostacyclin also decreased the amplitude of electrical slow waves and abolished action potentials. These electrical effects were associated with decreased contractile amplitude. It is concluded that the dominant prostaglandin responsible for the "prostaglandin effect" in canine ileal circular muscle must be inhibitory to spontaneous and acetylcholine-stimulated contractions. The mechanical effects attributed to endogenous prostaglandin appear to be due to an electrical mechanism. Based on the evidence presented prostacyclin emerges as the most likely candidate for the role of "dominant" prostaglandin, but PGE2 may also contribute as a modulator of electrical and mechanical activities.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000502:physiology; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D011460:Prostaglandins F / Q000378:metabolism
D011453:Prostaglandins; D011460:Prostaglandins F; D015121:6-Ketoprostaglandin F1 alpha; D000109:Acetylcholine; D007213:Indomethacin