4-Methylumbelliferoneの鎮痙作用機序
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The present experiments were undertaken to investigate the mechanism of spasmolytic action of 4-methylumbelliferone (4-MU). It has been reported that the spasmolytic actions of trihydroxybenzene derivatives and trihydroxypropiophenone (THPP) in the biliary system are partially due to the inhibition of catechol-O-methyltrasferase (COMT) activity. On the other hand, resorcinol, a dihydroxybenzene isomer is used as a synthetic material for 4-MU. Utilizing epinephrine as a substrate and S-adenosylmethionine as a methyl donor, the effects of pyrogallol and 4-MU on rat liver COMT activity were determined. Pyrogallol showed inhibition of enzyme activity depending on the concentration added, however, 4-MU was ineffective at any concentration. Contractile responses of the isolated rabbit aorta to transmural electrical stimulation and exogenously applied epinephrine were potentiated by pretreatment with pyrogallol, but were rather inhibited at high concentrations of 4-MU. The phasic and tonic contractions in the isolated rabbit sphincter of Oddi induced by KCl in normal nutrient solution were little affected by either THPP or 4-MU in low concentrations, but were inhibited, in high concentrations. On the other hand, these contractions were inhibited by papaverine in any concentration, but not so by atropine. The contractile responses of the isolated rabbit sphincter of Oddi to CaCl2 and BaCl2 in Ca++ free medium were significantly inhibited by THPP, papaverine and 4-MU, but not so by atropine. The transmural electrical stimulation applied to the sphincter of Oddid caused contractions of the two components, the initial one during stimulation and the other following stimulation. These two components were inhibited by papaverine and 4-MU, depending on the concentration added, but were only slightly inhibited by THPP in high concentrations. It was observed, however, that atropine usually converted the initial component to a relaxation. The late component was unaffected by atropine. The mechanism of spasmolytic action of 4-MU has been discussed herein.
- 社団法人 日本薬理学会の論文
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