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.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa
D001575:Benzomorphans; D002121:Calcium Channel Blockers; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases