Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localized to presynaptic active zones of the mammalian central nervous system (CNS). To elucidate the mechanism of impaired reproductivity of mGluR7 knockout (KO) mice, we investigated sexual behavior in this line, which exhibits ejaculatory disorder, although with normal sexual motivation and erectile function. To identify the site of action within the CNS responsible for the effect of mGluR7 on ejaculation, we then used a para-chloroamphetamine (PCA)-induced ejaculation model. Intrathecal administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) into the lumbosacral spinal cord inhibited PCA-induced ejaculation. Immunohistochemistry revealed mGluR7-like immunoreactivity (LI) expressed in the same area where lumbar spinothalamic (LSt) cells regulate the parasympathetic ejaculatory pathway. At high magnification, the apposition of mGluR7-LI puncta and neuronal nitric oxide synthase (nNOS)-LI-positive putative parasympathetic preganglionic neurons was evident. These results indicate that mGluR7 in the lumbosacral spinal cord regulates ejaculation by potentiating the excitability of parasympathetic preganglionic neurons. The ejaculatory disorder is a major issue in the field of male reproductive function. Erectile dysfunction (ED) can be treated by phosphodiesterase type 5 inhibitors like sildenafil (Viagra®), but the ejaculatory disorder cannot. Lack of understanding of the ejaculatory mechanism hinders the development of therapies for ejaculatory problems. This study is the first to demonstrate that mGluR7 regulates ejaculation and the results provide insight into the mechanism of ejaculation as well as a strategy for future therapies to treat ejaculatory disorders in humans.

代谢型谷氨酸受体亚型7（mGluR7）是III型mGluRs的成员，它们通过Gi / Go蛋白与腺苷酸环化酶负偶联，并位于哺乳动物中枢神经系统（CNS）的突触前活动区。为了阐明mGluR7基因敲除（KO）小鼠生殖能力受损的机制，我们调查了这行表现出射精障碍的性行为，尽管该行为具有正常的性动机和勃起功能。为了识别CNS负责mGluR7对射精的影响范围内采取行动的现场，我们又用对-氯苯丙胺（PCA）诱导的射精模型。将鞘内注射mGluR7选择性拮抗剂6-（4-甲氧基苯基）-5-甲基-3-吡啶-4-基异唑[4,5-c]吡啶-4（5H）-一（MMPIP）注入腰s脊髓抑制了PCA诱导的射精。免疫组织化学显示，在腰椎道（LSt）细胞调节副交感性射精途径的同一区域表达了mGluR7样免疫反应（LI）。在高放大倍数下，mGluR7-LI点和神经元一氧化氮合酶（nNOS）-LI阳性的假定副交感神经节前神经元并存。这些结果表明腰s脊髓中的mGluR7通过增强副交感神经节前神经元的兴奋性来调节射精。射精障碍是男性生殖功能领域的主要问题。勃起功能障碍（ED）可以通过5型磷酸二酯酶抑制剂西地那非（Viagra®）来治疗，但射精障碍则不能。对射精机制缺乏了解阻碍了射精问题疗法的发展。这项研究是第一个证明mGluR7调节射精的方法，其结果提供了对射精机理的了解以及未来治疗人类射精障碍的策略。