Auzanneau Céline, Norez Caroline, Antigny Fabrice, Thoreau Vincent, Jougla Chantal, Cantereau Anne, Becq Frédéric, Vandebrouck Clarisse
Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, CNRS, 40 avenue du recteur Pineau, 86022 Poitiers, France.
Biochem Pharmacol. 2008 Jan 15;75(2):476-83. doi: 10.1016/j.bcp.2007.09.004. Epub 2007 Sep 8.
Sertoli cells provide a controlled microenvironment for regulation and maintenance of spermatogenesis for which an acidic milieu is crucial for male fertility. Sertoli cells also contribute to protection of spermatogenetic cells. Here, we showed that TRPV1 is expressed in rat Sertoli cells and regulates an acid sensing Cl(-) channel (ASCC). The expression of TRPV1 in rat Sertoli cells was demonstrated by RT-PCR, immunostaining and calcium measurement experiments. ASCC activity was inhibited by capsaicin (IC(50)=214.3+/-1.6 nM), olvanil (IC(50)=400+/-1.7 pM) and resiniferatoxin (IC(50)=9.3+/-1.5 nM) but potentiated by capsazepine (EC(50)=5.3+/-1.3 microM) and ruthenium red (EC(50)=2.3+/-1.5 microM). In the human airway epithelial cell line Calu-3 in which ASCC can be detected but not TRPV1, capsaicin and capsazepine were without any effect. Finally the application of the non-steroidal anti-inflammatory drug ibuprofen prevented the control of ASCC by TRPV1. Our study provides the first evidence for a regulation by TRPV1 of an acid sensing chloride channel in rat Sertoli cells. TRPV1 and ASCC may thus be considered as new potential physiological regulators of spermatogenesis and targets for pharmacological treatments of reproductive disorders as cryptorchidism, Sertoli cell tumors or torsion of the spermatic cord.
支持细胞为精子发生的调节和维持提供了一个可控的微环境,其中酸性环境对男性生育能力至关重要。支持细胞也有助于保护生精细胞。在此,我们表明瞬时受体电位香草酸亚型1(TRPV1)在大鼠支持细胞中表达,并调节一种酸敏感氯离子通道(ASCC)。通过逆转录聚合酶链反应(RT-PCR)、免疫染色和钙测量实验证实了TRPV1在大鼠支持细胞中的表达。辣椒素(IC50=214.3±1.6 nM)、奥伐尼(IC50=400±1.7 pM)和树脂毒素(IC50=9.3±1.5 nM)可抑制ASCC活性,但辣椒平(EC50=5.3±1.3 μM)和钌红(EC50=2.3±1.5 μM)可增强其活性。在可检测到ASCC但未检测到TRPV1的人气道上皮细胞系Calu-3中,辣椒素和辣椒平没有任何作用。最后,应用非甾体抗炎药布洛芬可阻止TRPV1对ASCC的调控。我们的研究首次证明了TRPV1对大鼠支持细胞中酸敏感氯离子通道的调控作用。因此,TRPV1和ASCC可能被视为精子发生的新的潜在生理调节因子以及隐睾症、支持细胞瘤或精索扭转等生殖系统疾病药物治疗的靶点。