L-type Ca2+ channel ligands modulate morphine effects on the hypothalamus-pituitary-adrenocortical axis in rats.
The role of the L-type Ca2+ channel in the acute effects of morphine on the hypothalamo-pituitary-adrenocortical (HPA) system was studied by administration of the Ca2+ channel agonist, BAY K 8644, and the antagonists, verapamil and nimodipine, to rats. Morphine (30 mg/kg i.p.) induced an increase in corticosterone secretion 30 min after injection, which was correlated with a simultaneous change in hypothalamic noradrenaline (NA) and dopamine (DA) contents. Pretreatment with verapamil (10 or 20 mg/kg i.p.) or nimodipine (5 mg/kg i.p.) antagonized the HPA activation induced by morphine, blocking both the decrease in hypothalamic NA levels and the elevation in plasma corticosterone induced by the opioid. BAY K 8644 (2 mg/kg i.p.) potentiated the effects of morphine, decreasing the hypothalamic NA content and increasing the release of corticosterone. The Ca2+ channel antagonist, nimodipine, given alone induced a slight reduction in hypothalamic NA content but did not modify plasma corticosterone levels. Verapamil given alone did not alter HPA activity. Instead, the Ca2+ agonist decreased the hypothalamic catecholamine content and increased plasma corticosterone levels. These results indicate that Ca2+ influx is necessary for the expression of opioid actions on the HPA system, and suggest that the Ca2+ flux in hypothalamic neurons is functionally linked to activation of opioid receptors.
Martinez-Piñero
M G
MG
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
Vargas
M L
ML
Milanés
M V
MV
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009020:Morphine; D014700:Verapamil; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine