Yamada Yuko, Ohinata Kousaku, Lipkowski Andrzej W, Yoshikawa Masaaki
Kyoto University, Uji, Japan.
Peptides. 2009 Apr;30(4):735-9. doi: 10.1016/j.peptides.2008.11.011. Epub 2008 Nov 25.
Novokinin (Arg-Pro-Leu-Lys-Pro-Trp) is a vasorelaxing and hypotensive peptide acting through the angiotensin AT(2) receptor. Centrally administrated novokinin (30nmol/mouse) inhibited the antinociceptive effect of micro agonist morphine in mice, as evaluated by the tail-pinch test. The anti-opioid effect of novokinin was blocked by PD123319, an antagonist of the AT(2) receptor. Angiotensin II (0.01nmol/mouse, i.c.v.) and [p-aminophenylalanine(6)]-angiotensin II [p-NH(2)Phe(6)]-Ang II (0.1nmol/mouse, i.c.v.), a highly selective AT(2) receptor agonist, also inhibited the antinociceptive effect of morphine, and the effects were also blocked by PD123319. Angiotensin II did not suppress the antinociceptive effect induced by kappa or delta agonists. Novokinin, angiotensin II and [p-NH(2)Phe(6)]-Ang did not have affinity for the micro receptor. The anti-opioid effects induced by these peptides were blocked by ONO-AE3-240, an antagonist of the EP(3) receptor. These results suggest that the anti-opioid effects of AT(2) agonists are mediated by the PGE(2)-EP(3) receptor system downstream of the AT(2) receptor.
新激肽（精氨酸 - 脯氨酸 - 亮氨酸 - 赖氨酸 - 脯氨酸 - 色氨酸）是一种通过血管紧张素AT(2)受体发挥作用的血管舒张和降压肽。通过夹尾试验评估，向小鼠中枢给予新激肽（30纳摩尔/小鼠）可抑制微量激动剂吗啡的抗伤害感受作用。新激肽的抗阿片样物质作用被AT(2)受体拮抗剂PD123319阻断。血管紧张素II（0.01纳摩尔/小鼠，脑室内注射）和[对氨基苯丙氨酸(6)] - 血管紧张素II [p - NH(2)Phe(6)] - Ang II（0.1纳摩尔/小鼠，脑室内注射），一种高度选择性的AT(2)受体激动剂，也抑制了吗啡的抗伤害感受作用，且这些作用也被PD123319阻断。血管紧张素II并未抑制κ或δ激动剂诱导的抗伤害感受作用。新激肽、血管紧张素II和[p - NH(2)Phe(6)] - Ang对μ受体没有亲和力。这些肽诱导的抗阿片样物质作用被EP(3)受体拮抗剂ONO - AE3 - 240阻断。这些结果表明，AT(2)激动剂的抗阿片样物质作用是由AT(2)受体下游PGE(2) - EP(3)受体系统介导的。
