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  • Title: Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells of guinea pig cecum.
    Author: Okabe H, Chijiiwa Y, Nakamura K, Yoshinaga M, Akiho H, Harada N, Nawata H.
    Journal: Gastroenterology; 1995 Jan; 108(1):51-7. PubMed ID: 7806063.
    Abstract:
    BACKGROUND/AIMS: The functional receptors for endothelin (ET) in colonic smooth muscle are still unknown. This study investigated the expression of ET receptors in isolated circular smooth muscle cells of guinea pig cecum. METHODS: Inhibition of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin 6c (S6c), and ETA antagonists. Expression of the ET-receptor message was investigated using reverse-transcription polymerase chain reaction. The contractile potency of the ET family and the inhibitory effect of ETA antagonists on ET-1-induced contraction were also investigated. RESULTS: Unlabeled ET-1, ET-2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration-dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET-1 and ET-2. At a 10(-6) mol/L concentration of S6c, the specific binding of 125I-ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase chain reaction products for both the ETA and the ETB message were observed. ET-1 and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced contractions were significantly less potent than the ET-1-induced contraction. A significant response to S6c was obtained at a concentration as low as 10(-10) mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1-induced contraction. CONCLUSIONS: The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes.
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