V_2加压素受体拮抗剂SK&F105494对猪子宫肌催产素受体的阻断作用(英文)

SK&F 105494 a V_2-vasopressin receptor antagonist blocks oxytocin receptors in porcine myometrium

目的:确定V_2加压素受体拮抗剂SK&F105494(SK&F)对催产素受体的阻断作用。方法:采用猪离体子宫收缩试验和受体结合试验。结果:SK&F对赖氨酸加压素(Lyp)和催产素(Oxy)引起的子宫收缩均有阻断作用,并随SK&F浓度增加而加强。K_i值小于Lyp,近似于Oxy受体特异性阻断剂L-366948,分别为1.73±0.32,14.36±1.73和1.79±0.35nmol·L^(-1)。结论:SK&F对Oxy受体有强烈的阻断作用。

AIM: To study the effects of SK&F 106494 (SK&F), a V2-vasopressin receptor antagonist, on lypressin (Lyp)- and oxytocin (Oxy)-induced increases in myometrial contractility. METHODS: Uterine strips isolated from sows in the luteal phase of the estrous cycle were used to study the contractility. The receptor binding assays were performed to study the Oxy receptor blocking activity. RESULTS: Lyp and Oxy caused a concentration-dependent increase in myometrial contractility with EC50 of 50± 14 nmol·L-1 and 170 ±32 pmol·L-1, respectively. SK&F 30-300 nmol · L-1 antagonized the contractile effects of Lyp and Oxy in a concentration-dependent manner. When the concentration-dependent inhibition of [3H] Oxy binding by SK&F was compared with Lyp and L-366948 [(cyclo-(L-Pro-D-2-naphthyl-Ala-L-lle-D-pipecolic acid-L-pipecolic acid-D-His)], a potent antagonist specific for Oxy receptors, the K, values for SK&F, Lyp, and L-366948 were 1.73±0.32, 14.36±1.73, and 1.79 ±0.35 nmol · L-1, respectively. CONCLUSION: SK&F has a potent Oxy receptor blocking activity in addition to its known V2-receptor blocking activity.