Sheng Yinglun, Wang Ling, Liu X Shawn, Montplaisir Véronique, Tiberi Mario, Baltz Jay M, Liu X Johné
Ottawa Health Research Institute, Ottawa Hospital, Ottawa, Canada.
J Cell Physiol. 2005 Mar;202(3):777-86. doi: 10.1002/jcp.20170.
Accumulating evidence has indicated that vertebrate oocytes are arrested at late prophase (G2 arrest) by a G protein coupled receptor (GpCR) that activates adenylyl cyclases. However, the identity of this GpCR or its regulation in G2 oocytes is unknown. We demonstrated that ritanserin (RIT), a potent antagonist of serotonin receptors 5-HT2R and 5-HT7R, released G2 arrest in denuded frog oocytes, as well as in follicle-enclosed mouse oocytes. In contrast to RIT, several other serotonin receptor antagonists (mesulergine, methiothepine, and risperidone) had no effect on oocyte maturation. The unique ability of RIT, among serotonergic antagonists, to induce GVBD did not match the antagonist profile of any known serotonin receptors including Xenopus 5-HT7R, the only known G(s)-coupled serotonin receptor cloned so far in this species. Unexpectedly, injection of x5-HT7R mRNA in frog oocytes resulted in hormone-independent frog oocyte maturation. The addition of exogenous serotonin abolished x5-HT7R-induced oocyte maturation. Furthermore, the combination of x5-HT7R and exogenous serotonin potently inhibited progesterone-induced oocyte maturation. These results provide the first evidence that a G-protein coupled receptor related to 5-HT7R may play a pivotal role in maintaining G2 arrest in vertebrate oocytes.
越来越多的证据表明，脊椎动物的卵母细胞在前期晚期（G2期阻滞）被一种激活腺苷酸环化酶的G蛋白偶联受体（GpCR）所阻滞。然而，这种GpCR的身份及其在G2期卵母细胞中的调节机制尚不清楚。我们证明，利坦色林（RIT），一种强效的5-羟色胺受体5-HT2R和5-HT7R拮抗剂，能解除裸蛙卵母细胞以及卵泡包被的小鼠卵母细胞的G2期阻滞。与RIT不同，其他几种5-羟色胺受体拮抗剂（美舒麦角、甲硫噻嗪和利培酮）对卵母细胞成熟没有影响。在5-羟色胺能拮抗剂中，RIT诱导生发泡破裂（GVBD）的独特能力与任何已知的5-羟色胺受体的拮抗剂特征都不匹配，包括非洲爪蟾5-HT7R，这是该物种迄今为止唯一克隆的已知与G(s)偶联的5-羟色胺受体。出乎意料的是，在蛙卵母细胞中注射x5-HT7R mRNA导致激素非依赖性的蛙卵母细胞成熟。添加外源性5-羟色胺可消除x5-HT7R诱导的卵母细胞成熟。此外，x5-HT7R与外源性5-羟色胺的组合可有效抑制孕酮诱导的卵母细胞成熟。这些结果提供了首个证据，表明一种与5-HT7R相关的G蛋白偶联受体可能在维持脊椎动物卵母细胞的G2期阻滞中起关键作用。
