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KMID : 0360419800160010041
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Korean Journal of Pharmacology
1980 Volume.16 No. 1 p.41 ~ p.50
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The Effects of Cholates on Smooth Muscle Strips and Cardiac Muscle
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Abstract
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Chenodeoxycholic acid(CDCA) has been used as a gallstone dissolving agent since 1972. Recently, ursodeoxycholic acid(UDCA) has been reported to be effective in dissolving gallstones. Both bile acids increased bile flow. The increase in bile flow associated with an increase in cholesterol level in bile after CDCA or UDCA infusion was reported.
In this study, using the smooth muscle strips of guinea pig and fowl, responses of the cholates were observed. In addition, the influence of adrenergic blocking agents on the response of the strips to cholates was investigated. Also the effects of cholates on cardiac function were examined by using isolated atria of rabbit and heart of anesthetized frog.
The results are as follows:
1) All cholates, such as UDCA, CDCA, and CA produced a marked inhibitory effect on the motility in isolated duodenal strip of guinea pig and fowl, however, only UDCA showed the contraction in the isolated esophagus of fowl. These effects of cholates were blocked by propranolol.
2) In isolated guinea pig stomach strip and gall bladder, cholates exhibited a marked inhibitory effect on the motility and the effects due to UDCA and CA were blocked by phenoxybenzamine while CDCA was not affected.
3) The spontaneous and ouabain induced arrhythmia was partially abolished by cholates. However, concomitant administration of cholates with ouabain or epinephrine caused a marked prolongation in occurrence of atrial arrhythmia in comparison with ouabain or epinephrine alone in isolated rabbit atria.
4) In the heart of anesthetized frog, the epinephrine-induced arrhythmia was partially abolished by cholates. The combined treatment with cholates and ouabain or epinephrine produced a marked prolongation in occurrence of the arrhythmia in comparison with, ouabain or epinephrine alone.
From the above results, it can be suggested that the effects of cholates on the smooth muscle of duodenum and esophagus are produced in response to adrenergic ß-receptor and the effect or gall bladder and stomach is more likely due to the direct effect on the muscle. In addition, cholates exhibit a slight antiarrhythmic effect on heart, therefore, cholates can be classified as a nonselective antiarrhythmic drug, such as propranolol.
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