Cetin Ali, Kaya Tijen, Demirkoprulu Nihal, Karadas Baris, Duran Bulent, Cetin Meral
Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey.
J Pharmacol Sci. 2004 Jan;94(1):19-24. doi: 10.1254/jphs.94.19.
The aim of this study was to investigate the effect of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole) on spontaneous contractions and levels of cyclic GMP (cGMP) of myometrial strips isolated from pregnant rats. It is a nitric oxide-independent soluble guanylate cyclase activator. Myometrial strips were obtained from eight pregnant Wistar albino rats and were mounted in organ baths for the recording of isometric tensions. We evaluated the effect of increasing concentrations of YC-1 on spontaneous myometrial contractions and on contractions of myometrial smooth muscle pretreated with methylene blue (10(-5) M), tetraethylammonium chloride (TEA) (3 x 10(-4) M), and glibenclamide (10(-6) M). YC-1 (10(-9) - 3 x 10(-5) M) concentration-dependently decreased the amplitude and frequency of spontaneous contractions of myometrial strips. The inhibition of the amplitude and frequency of spontaneous contractions by YC-1 were antagonized with methylene blue (10(-5) M) and TEA (3 x 10(-4) M), but they were not changed by glibenclamide (10(-6) M); however, the antagonistic effect of methylene blue was significantly more than that of TEA (P<0.05). We also evaluated the effect of YC-1 on the levels of cGMP in myometrial strips obtained from pregnant rat uterine horns. YC-1-stimulated myometrial strips showed an excessive elevation in myometrial cGMP that declined slowly during the subsequent washout period. These results show that YC-1 decreases spontaneous contractile activity of myometrial strips isolated from pregnant rat and causes elevation of myometrial cGMP levels in vivo. This effect of YC-1 is significantly reduced by the methylene blue and TEA, suggesting the activation of soluble guanylate cyclase and Ca(2+)-sensitive K(+) channels as the mechanisms of action.
本研究旨在探讨YC-1（3-(5'-羟甲基-2'-呋喃基)-1-苄基吲唑）对从妊娠大鼠分离的子宫肌条自发收缩及环磷酸鸟苷（cGMP）水平的影响。它是一种不依赖一氧化氮的可溶性鸟苷酸环化酶激活剂。从8只妊娠的Wistar白化大鼠获取子宫肌条，并将其安装在器官浴槽中以记录等长张力。我们评估了不同浓度的YC-1对子宫肌条自发收缩以及对用亚甲蓝（10(-5) M）、四乙铵（TEA）（3×10(-4) M）和格列本脲（10(-6) M）预处理的子宫肌平滑肌收缩的影响。YC-1（10(-9) - 3×10(-5) M）浓度依赖性地降低子宫肌条自发收缩的幅度和频率。亚甲蓝（10(-5) M）和TEA（3×10(-4) M）可拮抗YC-1对自发收缩幅度和频率的抑制作用，但格列本脲（10(-6) M）对其无影响；然而，亚甲蓝的拮抗作用显著强于TEA（P<0.05）。我们还评估了YC-1对从妊娠大鼠子宫角获取的子宫肌条中cGMP水平的影响。YC-1刺激的子宫肌条显示子宫肌cGMP过度升高，且在随后的洗脱期缓慢下降。这些结果表明，YC-1降低从妊娠大鼠分离的子宫肌条的自发收缩活性，并在体内导致子宫肌cGMP水平升高。亚甲蓝和TEA可显著降低YC-1的这种作用，提示可溶性鸟苷酸环化酶和钙敏感钾通道的激活是其作用机制。
