Cario-Toumaniantz C, Loirand G, Ladoux A, Pacaud P
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, Valbonne, France.
Circ Res. 1998 Jul 27;83(2):196-203. doi: 10.1161/01.res.83.2.196.
In cutaneous veins where purinergic neurotransmission is more prominent compared with in deep vessels, physiological and pathological roles of nerve-released ATP have been described. Neuronally released ATP has been reported to act through activation of unidentified ionotropic P2X receptor(s). This study analyzed P2X receptor subtypes expressed in human saphenous vein smooth muscle and their physiological functions. Transcripts for both hP2X1 receptors, already identified in other smooth muscles, and, surprisingly, hP2X7 receptors known to be responsible for the cytotoxic effect of ATP in macrophages were detected by Northern blot analysis in total RNA from saphenous vein smooth muscle. ATP and other P2X receptor agonists [alphabeta-methylene-ATP, 2-methylthio-ATP, and 2',3'-(4-benzoyl)benzoyl-ATP] dose-dependently contracted venous rings, but the contraction induced by 2-methylthio-ATP was more transient than that evoked by the other P2X agonists. The effect of hP2X1 agonists involved the activation of a rapidly desensitizing cation current recorded in freshly isolated myocytes. The action of hP2X7 receptor agonists was related to a maintained nondesensitizing cation current. In addition, hP2X7 receptor activation formed membrane pores that were permeable to large molecules. hP2X1 and hP2X7 receptors coexpressed in COS cells did not associate to form heteromultimers. Our data indicate that both hP2X1 and hP2X7 receptors are expressed as 2 separated populations of channels in human saphenous vein myocytes and are involved in ATP-induced tension. We suggest that cell lysis consequent to hP2X7 receptor-induced pore formation contributes to the disorganization and decrease in the amount of contractile myocytes in the media of varicose veins.
与深部血管相比，嘌呤能神经传递在皮肤静脉中更为显著，神经释放的ATP在其中的生理和病理作用已有描述。据报道，神经元释放的ATP通过激活未明确的离子型P2X受体发挥作用。本研究分析了人隐静脉平滑肌中表达的P2X受体亚型及其生理功能。通过Northern印迹分析，在隐静脉平滑肌的总RNA中检测到了已在其他平滑肌中鉴定出的hP2X1受体转录本，令人惊讶的是，还检测到了已知在巨噬细胞中负责ATP细胞毒性作用的hP2X7受体转录本。ATP和其他P2X受体激动剂[αβ-亚甲基-ATP、2-甲硫基-ATP和2',3'-(4-苯甲酰基)苯甲酰基-ATP]能使静脉环剂量依赖性收缩，但2-甲硫基-ATP诱导的收缩比其他P2X激动剂引起的收缩更短暂。hP2X1激动剂的作用涉及激活在新鲜分离的心肌细胞中记录到的快速脱敏阳离子电流。hP2X7受体激动剂的作用与持续的非脱敏阳离子电流有关。此外，hP2X7受体激活形成了对大分子通透的膜孔。在COS细胞中共表达的hP2X1和hP2X7受体不会缔合形成异源多聚体。我们的数据表明，hP2X1和hP2X7受体在人隐静脉心肌细胞中作为两个分离的通道群体表达，并参与ATP诱导的张力。我们认为，hP2X7受体诱导的孔形成导致的细胞裂解有助于静脉曲张中膜收缩性心肌细胞的紊乱和数量减少。
