Ambriz-Tututi Mónica, Velázquez-Zamora Dulce A, Urquiza-Marín Héctor, Granados-Soto Vinicio
Escuela de Químico-Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
Eur J Pharmacol. 2005 Apr 11;512(2-3):121-7. doi: 10.1016/j.ejphar.2005.01.055.
The mechanism of the antinociceptive action of the phosphodiesterase 5 inhibitor, sildenafil, was assessed in the formalin test. Local peripheral ipsilateral, but not contralateral, administration of sildenafil (50-200 microg/paw) produced a dose-related antinociception during both phases of the formalin test. The local peripheral pretreatment with protein kinase G inhibitor peptide (PKG inhibitor, 0.01-1 microg/paw), charybdotoxin (large- and intermediate-conductance Ca2+-activated K+ channel blocker, 0.01-1 microg/paw), apamin (small-conductance Ca2+-activated K+ channel blocker, 0.1-2 microg/paw), tolbutamide (ATP-sensitive K+ channel blocker, 12.5-50 microg/paw), and tetraethylammonium (non-selective voltage-dependent K+ channel blocker, 12.5-50 microg/paw), but not 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, inhibitor of guanylyl cyclase, 12.5-50 microg/paw) or saline, significantly diminished in a dose-dependent manner sildenafil-induced local peripheral antinociception. Given alone, local peripheral administration of inhibitors did not modify formalin-induced nociceptive behavior. Results suggest that sildenafil produces its local peripheral antinociceptive effect via activation of the cyclic GMP-PKG-K+ channel pathway.
在福尔马林试验中评估了磷酸二酯酶5抑制剂西地那非的抗伤害感受作用机制。在福尔马林试验的两个阶段，于同侧而非对侧局部外周给予西地那非（50 - 200微克/爪）可产生剂量相关的抗伤害感受作用。用蛋白激酶G抑制剂肽（PKG抑制剂，0.01 - 1微克/爪）、卡律蝎毒素（大电导和中电导Ca2+激活的K+通道阻滞剂，0.01 - 1微克/爪）、蜂毒明肽（小电导Ca2+激活的K+通道阻滞剂，0.1 - 2微克/爪）、甲苯磺丁脲（ATP敏感性K+通道阻滞剂，12.5 - 50微克/爪）和四乙铵（非选择性电压依赖性K+通道阻滞剂，12.5 - 50微克/爪）进行局部外周预处理，但不包括1H-(1,2,4)-恶二唑并(4,2-a)喹喔啉-1-酮（ODQ，鸟苷酸环化酶抑制剂，12.5 - 50微克/爪）或生理盐水，可显著剂量依赖性地减弱西地那非诱导的局部外周抗伤害感受作用。单独给予时，局部外周给予抑制剂不会改变福尔马林诱导的伤害感受行为。结果表明，西地那非通过激活环磷酸鸟苷 - PKG - K+通道途径产生其局部外周抗伤害感受作用。
