摘出モルモット胆のうにおける胆汁酸塩の作用について

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Inhibitory activities of four bile salts, deoxycholate, chenodeoxycholate, ursodeoxy-cholate and cholate on the cholecystokinin (CCK)- and acetylcholine (ACh)-induced contraction of the isolated guinea-pig gallbladder were compared. K_i values of bile salts for the CCK-induced contraction were not different from those of the corresponding bile salts for ACh-induced contraction. Deoxycholate inhibited the maximum response of the gallbiadder to CCK and ACh in a similar manner. Potassium chloride-induced contraction was also inhibited by these bile salts. These findings indicate that bile salts exert a nonspecific inhibitory effect on the contractility of gallbladder. Anti-CCK activities of conjugated bile salts were also examined but their activities were found to be much lower than those of the corresponding bile salts. Imidazole, a phosphodiesterase (PDE) activator, significantly reduced the anti-CCK action of deoxycholate. Inhibitory actions of deoxycholate and dibutyryl cyclic adenosine monophosphate (c-AMP) on the potassium chlorideinduced contraction disappeared in the absence of external sodium ion but were readily restored by the addition of 10mM sodium ion to the bathing solution. These facts suggest that bile salts exert their spasmolytic action in gallbladder by inhibiting PDE and resulting accumulation of cyclic AMP, as proposed by Uruno et al. in rat uterus. Meanwhile, imidazole supra-additively enhanced the contractile action of CCK. This findings may argue against the concept proposed by Amer that CCK induces contraction of gallbladder via activating PDE of the muscle.
公益社団法人日本薬学会の論文
1984-10-25

摘出モルモット胆のうにおける胆汁酸塩の作用について

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