D'Amico M, Di Filippo C, Rossi F
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, II University of Naples, Italy.
Life Sci. 1997;61(25):PL 397-401. doi: 10.1016/s0024-3205(97)00988-0.
The injection of endothelin-1 (ET-1) (2 pmol) into the dorsolateral periaqueductal gray area (PAG) of mice produces antinociceptive effect as underscored by increases in the latency time for the reaction to a hot plate. Pretreatment of the PAG area with bosentan (10 nmol) (a mixed ET(A)/ET(B) receptor antagonist), FR 139317 (5 nmol) (ET[A] receptor selective antagonist) or BQ-788 (5 nmol) (ET[B] receptor selective antagonist) greatly reduced the antinociceptive effect induced by ET-1. Therefore, ET-1 induces antinociceptive effects via both ET(A)/ET(B) receptors. In addition, since ET-antagonists lowered per se the control reaction time of the mice when administered alone to the PAG area, we would suggest that endogenous ET-1 acting within the PAG area contributes to the suppression of pain.
向小鼠背外侧导水管周围灰质区域（PAG）注射内皮素-1（ET-1）（2皮摩尔）可产生抗伤害感受作用，热板反应潜伏期延长即突出显示了这一点。用波生坦（10纳摩尔）（一种ET（A）/ET（B）混合型受体拮抗剂）、FR 139317（5纳摩尔）（ET（A）受体选择性拮抗剂）或BQ-788（5纳摩尔）（ET（B）受体选择性拮抗剂）对PAG区域进行预处理，可大大降低ET-1诱导的抗伤害感受作用。因此，ET-1通过ET（A）/ET（B）受体诱导抗伤害感受作用。此外，由于ET拮抗剂单独施用于PAG区域时本身会降低小鼠的对照反应时间，我们认为PAG区域内起作用的内源性ET-1有助于疼痛抑制。
