title: Inhibition by free radical scavengers and by cyclooxygenase inhibitors of the effect of acidosis on calcium transport by masseter muscle sarcoplasmic reticulum.
abstract: In vitro, arachidonic acid depressed calcium transport by sarcoplasmic reticulum (SR) in the homogenate of canine masseter muscle. This effect was inhibited by superoxide dismutase (SOD), a scavenger of the superoxide anion radial ( . O-2), at pH 7.0, and by SOD plus d-mannitol, a scavenger of hydroxyl free radical ( . OH), at pH 5.5. Indomethacin and 2-aminomethyl-4-tert-butyl-6-propionyl phenol (ONO-3144), a compound known to accelerate the conversion of prostaglandin G2 (PGG2) to PGH2 and scavenge free radicals, inhibited the effect of arachidonic acid at both pH 7.0 and pH 5.5. PGG2, but not PGH2, duplicated the effect of arachidonic acid. The effect of PGG2 on SR function was similar to that of exogenous free radicals generated from the xanthine-xanthine oxidase system. Incubation at pH 5.5, in the absence of an exogenous free-radical generating system, depressed SR calcium transport in the homogenate and in isolated SR. This effect in the homogenate was inhibited by indomethacin or by ONO-3144. At 10-min incubation at pH 5.5, SOD partially and temporarily reversed the depressant effect of acidosis. The addition of SOD plus d-mannitol completely reversed the system. d-Mannitol alone was ineffective. Arachidonic acid was able to mimic these effects of acidosis, except that arachidonic acid further depressed isolated SR calcium transport. These results demonstrate that acidosis can depress SR calcium transport in the homogenate of masseter muscle by an oxygen-free radical mechanism by the generation of . O-2 and . OH. Our results also demonstrate that significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism at an acidotic pH in the cellular environment outside of the SR of the muscle cell, and seems to be responsible for the generation of the . OH derived from . O-2.
authors.forename: E
authors.initials: E
authors.lastname: Okabe
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Kohno
authors.forename: M L
authors.initials: ML
authors.lastname: Hess
authors.forename: H
authors.initials: H
authors.lastname: Ito
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008406:Masseter Muscle / Q000378:metabolism*; D008410:Masticatory Muscles / Q000378:metabolism*; D011427:Propiophenones / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D011427:Propiophenones; D013481:Superoxides; D016718:Arachidonic Acid; D008353:Mannitol; C037467:2-aminomethyl-4-tert-butyl-6-propionylphenol; D013482:Superoxide Dismutase; D002118:Calcium; D007213:Indomethacin