Pillai N P, Ross D H
Eur J Pharmacol. 1986 Dec 16;132(2-3):237-44. doi: 10.1016/0014-2999(86)90610-2.
Administration of the opiate U-50,488H (3-20 mg/kg s.c.), a selective kappa receptor agonist, produced a dose-dependent decrease of rectal temperature in rats. This hypothermic effect of U-50,488H was accompanied by an enhanced activity of Ca2+/Mg2+ ATPase in crude synaptosomal (P2) fractions obtained from hypothalamus but not from cortex or cerebellum. Mg2+ ATPase activity in these regions was not altered by U-50,488H (15 mg/kg s.c.). Naloxone (5 mg/kg) partially and MR2266 (5 mg/kg) completely reversed the temperature and enzyme changes. Pretreatment with the calcium channel blockers nimodipine (1 mg/kg s.c.), diltiazem (10 mg/kg s.c.) and verapamil (2.5 mg/kg s.c.) potentiated the hypothermic effect of U-50,488H as well as the stimulation of Ca2+/Mg2+ ATPase in hypothalamus. These observations suggest that kappa agonists may produce opiate receptor mediated hypothermia through changes in intracellular Ca2+ levels in the hypothalamus.
给予阿片类物质U - 50,488H（皮下注射3 - 20毫克/千克），一种选择性κ受体激动剂，可使大鼠直肠温度呈剂量依赖性降低。U - 50,488H的这种降温作用伴随着从下丘脑而非皮质或小脑中获得的粗制突触体（P2）组分中Ca2+/Mg2+ ATP酶活性增强。U - 50,488H（皮下注射15毫克/千克）未改变这些区域的Mg2+ ATP酶活性。纳洛酮（5毫克/千克）部分逆转且MR2266（5毫克/千克）完全逆转了温度和酶的变化。用钙通道阻滞剂尼莫地平（皮下注射1毫克/千克）、地尔硫䓬（皮下注射10毫克/千克）和维拉帕米（皮下注射2.5毫克/千克）预处理可增强U - 50,488H的降温作用以及对下丘脑Ca2+/Mg2+ ATP酶的刺激。这些观察结果表明，κ激动剂可能通过改变下丘脑细胞内Ca2+水平产生阿片受体介导的体温过低。
