Endothelin-1 induces contraction of human and Australian possum gallbladder in vitro
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BACKGROUND: Endothelin-1 (ET-1) stimulates guinea pig gallbladder (GB) muscle strip contractility; however, the role and source of ET-1 in the GB remains to be elucidated. AIMS: To determine the effect of ET-1 on human and possum GB muscle strip contractility and evaluate whether ET-1 is present in GB tissue. METHODS: GB muscle strips were mounted in organ baths to measure isometric tension. ET-1 was added cumulatively with and without pretreatment with the neural blocker tetrodotoxin (TTX) or the ET receptor antagonists BQ-123, BQ-788, and tezosentan. Immunohistochemical localization of ET was performed on freshly fixed and cultured GBs. RESULTS: ET-1 induced concentration-dependent increases in tone in human and possum GB strips (p<0.05). This response was unaffected by BQ-123, BQ-788, and TTX but antagonized by BQ-123+BQ-788 in the human tissue only. Tezosentan (10(-4) mol/l) blocked the ET-1-induced response in human and possum GB strips (p<0.001). Although ET immunoreactivity was absent in freshly fixed possum GB, immunoreactivity was observed in the GB epithelium of freshly fixed human tissue and in both possum and human tissue following 24 h of organ culture. CONCLUSION: ET-1 acts directly on human and possum GB smooth muscle producing contractions, possibly via ET-B receptors. ET may be present under pathophysiological conditions altering GB function.