title: Antagonism by manganese of isoprenaline dilatation of the guinea-pig isolated trachea.
abstract: Manganese (0.5-100 mumol/l) was found to be a potent inhibitor of the dilator effect of isoprenaline on the isolated tracheal muscle of the guinea-pig. Above these concentrations the inhibitory action of Mn2+ diminished and no inhibition occurred above 1000 mumol/l Mn2+. Thus a bell-shaped dose-response curve resulted for the inhibition of isoprenaline by Mn2+. The antagonism was surmountable but apparently noncompetitive. Dilation of the isolated trachea caused by theophylline or nitroprusside was not inhibited by Mn2+ at concentrations of 12.5 to 750 mumol/l. At the dose range which could be tested manganese did not antagonize isoprenaline bronchodilatation in vivo. However, manganese at doses between 0.5 and 2.0 mumol/kg inhibited increased in pulmonary resistance caused by acetylcholine, histamine or serotonin. At concentrations above 250 mumol/l Mn2+ inhibited constrictor responses to histamine, acetylcholine and serotonin in guinea-pig isolated ileum and trachea, and inhibited serotonin and prostaglandin E2 contractions in rat fundus. Co2+, Fe2+, Fe3+ and Zn2+ were also tested for their action against isoprenaline on the isolated trachea. Co2+ was similar in effect to Mn2+ but had only 1/50 of the potency. Up to the highest concentrations which could be tested, namely 1000 mumol/l, the other trace metals produced negligible effects. Thus Mn2+ showed selective inhibition of the relaxant effect of isoprenaline on the guinea-pig isolated trachea, at concentrations of Mn2+ well below those shown previously to inhibit constrictor responses by block of transmembrane Ca2+ entry. It is suggested that Mn2+ may interfere with intracellular Ca2+ fluxes in the isolated trachea.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D008168:Lung / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
chemical_list: D008345:Manganese; D006632:Histamine; D007501:Iron; D007545:Isoproterenol; D002118:Calcium