Monochloramine induces contraction of guinea pig gallbladder via two different pathways.
The purpose of the present investigation was to examine the effect and mechanism of action of the reactive oxygen metabolites monochloramine (NH2Cl), hypochlorous acid (HOCl), and hydrogen peroxide (H2O2) on gallbladder smooth muscle contractility. All oxidants caused concentration-dependent increases in resting tension of gallbladder muscle; the rank order of potencies (half-maximal concentration) was NH2Cl (30 microM) greater than HOCl (70 microM) greater than H2O2 (100 microM). The oxidant concentrations employed are those found to exist in inflamed tissue. Tetrodotoxin (0.5 microM) had no effect on gallbladder muscle contraction caused by the oxidants, suggesting a direct, nonneural action. The maximal response induced by NH2Cl, HOCl, or H2O2 was significantly (P less than 0.05) inhibited by 5 microM indomethacin and 5 microM piroxicam. The calcium channel blocker verapamil partially inhibited the contractile effect of NH2Cl but had no effect on the contraction induced by exogenous cyclooxygenase products. Monochloramine induced significant prostaglandin E2 release from the gallbladder, which was blocked by indomethacin. Furthermore, the effect of NH2Cl on the smooth muscle was blocked by 5-aminosalicylic acid (1 mM). We conclude that reactive oxygen metabolites induce contraction of gallbladder smooth muscle by a direct action. The effect is mediated via cyclooxygenase metabolites and activation of calcium influx.
Moummi
C
C
Division of Gastrointestinal Diseases, Searle Research and Development, Skokie, Illinois 60077.
Gullikson
G W
GW
Gaginella
T S
TS
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D002700:Chloramines / Q000494:pharmacology*; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D019804:Mesalamine; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010894:Piroxicam / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000636:Aminosalicylic Acids; D002700:Chloramines; D010566:Virulence Factors, Bordetella; D010894:Piroxicam; D013779:Tetrodotoxin; D019804:Mesalamine; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D014700:Verapamil; C030816:chloramine; D007213:Indomethacin