Jamieson D D, Quinn R J, le Coutier A
Clin Exp Pharmacol Physiol. 1983 Sep-Oct;10(5):511-9. doi: 10.1111/j.1440-1681.1983.tb00219.x.
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.
已发现锰（0.5 - 100微摩尔/升）是异丙肾上腺素对豚鼠离体气管肌舒张作用的强效抑制剂。高于这些浓度时，Mn2+的抑制作用减弱，在1000微摩尔/升Mn2+以上则无抑制作用。因此，Mn2+对异丙肾上腺素的抑制作用呈现钟形剂量 - 反应曲线。这种拮抗作用是可克服的，但显然是非竞争性的。在12.5至750微摩尔/升浓度下，Mn2+不抑制茶碱或硝普钠引起的离体气管舒张。在可测试的剂量范围内，锰在体内不拮抗异丙肾上腺素的支气管舒张作用。然而，0.5至2.0微摩尔/千克剂量的锰可抑制乙酰胆碱、组胺或5 - 羟色胺引起的肺阻力增加。在高于250微摩尔/升的浓度下，Mn2+抑制豚鼠离体回肠和气管对组胺、乙酰胆碱和5 - 羟色胺的收缩反应，并抑制大鼠胃底对5 - 羟色胺和前列腺素E2的收缩。还测试了Co2+、Fe2+、Fe3+和Zn2+对异丙肾上腺素在离体气管上的作用。Co2+的作用与Mn2+相似，但效力仅为其1/50。在可测试的最高浓度即1000微摩尔/升以下，其他痕量金属产生的影响可忽略不计。因此，在Mn2+浓度远低于先前显示通过阻断跨膜Ca2+内流抑制收缩反应的浓度时，Mn2+对异丙肾上腺素在豚鼠离体气管上的舒张作用表现出选择性抑制。提示Mn2+可能干扰离体气管中的细胞内Ca2+通量。
