Interaction of kappa receptor agonists with Ca2+ channel antagonists in the modulation of hypothermia

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.