Smith F L, Stevens D L
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond.
J Pharmacol Exp Ther. 1995 Jan;272(1):290-9.
Calcium (Ca++) administered into the i.c.v. space of mice has been reported to block opioid-induced antinociception dose dependently. These studies were conducted to test the hypothesis that Ca++ i.c.v. blocks the antinociceptive effects of morphine i.c.v. as a consequence of transmembrane Ca++ influx and Ca++ release from intracellular pools. Mice were injected with voltage-sensitive Ca++ channel antagonists at a dose that did not affect morphine antinociception to determine whether this pretreatment would prevent the inhibitory effects of Ca++. Nimodipine (12 nmol i.c.v.) was ineffective in preventing the inhibitory effects of Ca++ (100 nmol i.c.v.), whereas omega-conotoxin GVIA (3.3 pmol i.c.v.) completely prevented the inhibition by Ca++ of morphine antinociception. Other experiments were conducted to determine whether blocking Ca++ release from Ca++/caffeine-sensitive microsomal pools with ryanodine would prevent the inhibitory effects of Ca++. Ryanodine (2 nmol i.c.v.) significantly attenuated the inhibition by Ca++ of morphine antinociception. Another hypothesis to be tested was that stimulation of Ca++ release from intracellular pools would, like Ca++, block morphine antinociception. Thapsigargin (0.002-30 nmol i.c.v.), which increases cytosolic Ca++ by depleting Ca++ from inositol 1,4,5-trisphosphate-sensitive microsomal pools, dose-dependently blocked the antinociceptive effects of morphine. The results of this study indicate that Ca++ blocked morphine antinociception by stimulating Ca++ influx through omega-conotoxin GVIA-sensitive channels and by stimulating Ca++ release from Ca++/caffeine-sensitive microsomal pools.
据报道，向小鼠脑室内注射钙（Ca++）会剂量依赖性地阻断阿片类药物诱导的镇痛作用。进行这些研究是为了检验以下假设：脑室内注射Ca++会由于跨膜Ca++内流和细胞内钙库释放Ca++而阻断脑室内注射吗啡的镇痛作用。给小鼠注射对吗啡镇痛作用无影响剂量的电压敏感性Ca++通道拮抗剂，以确定这种预处理是否能预防Ca++的抑制作用。尼莫地平（脑室内注射12 nmol）未能预防Ca++（脑室内注射100 nmol）的抑制作用，而ω-芋螺毒素GVIA（脑室内注射3.3 pmol）则完全预防了Ca++对吗啡镇痛作用的抑制。进行了其他实验以确定用ryanodine阻断Ca++/咖啡因敏感微粒体钙库释放Ca++是否能预防Ca++的抑制作用。Ryanodine（脑室内注射2 nmol）显著减弱了Ca++对吗啡镇痛作用的抑制。另一个有待检验的假设是，刺激细胞内钙库释放Ca++会像Ca++一样阻断吗啡的镇痛作用。毒胡萝卜素（脑室内注射0.002 - 至30 nmol）通过耗尽肌醇1,4,5-三磷酸敏感微粒体钙库中的Ca++来增加胞质Ca++，剂量依赖性地阻断了吗啡的镇痛作用。本研究结果表明，Ca++通过刺激经ω-芋螺毒素GVIA敏感通道的Ca++内流以及刺激Ca++/咖啡因敏感微粒体钙库释放Ca++来阻断吗啡的镇痛作用。
