Activation of dihydropyridine receptors differentially regulates temperature responses in rat.
Rats receiving the dihydropyridine Ca++ agonist BAY K8644 (0.1-3 mg/kg SC) displayed increasing loss of body temperature. At the highest dose tested (3 mg/kg) rats exhibited decreased motor activity, ataxia, increased vocalization upon handling and increased auditory sensitivity. Nimodipine (1 mg/kg SC) produced antagonism of this response when used as pretreatment at 15 and 30 minutes. The phenylalkylamine, verapamil (5 mg/kg) and the benzothiazepine diltiazem (10 mg/kg) did not alter BAY K8644-induced hypothermia. None of the three Ca++ channel antagonists produced changes in body temperature at the antagonist doses used. BAY K8644 (3 mg/kg SC) produced stimulation of Ca++/Mg++ ATPase activity by 31% in hypothalamus but not in cortex or cerebellum. This stimulation of enzyme activity was selectively prevented by nimodipine but not verapamil or diltiazem. No changes in enzyme activity were observed when Ca++ channel antagonists were used alone. These studies demonstrate that the Ca++ agonist BAY K8644 produces receptor mediated hypothermia which is dihydropyridine receptor dependent. Activation of Ca++ ATPase in the hypothalamus suggests that activation of dihydropyridine receptors may be coupled to Ca++ transport systems in this brain region and may reinforce the Ca++ set point theory of thermoregulation.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases