Neuroendocrine effects of dexmedetomidine: evidence of cross-tolerance between a mu-opioid agonist and an alpha 2-adrenoceptor agonist in growth hormone secretion of the male rat.
The role of alpha 2-adrenergic receptors (adrenoceptors) in the secretion of growth hormone, prolactin and thyrotropin was studied using highly selective agonists and antagonists of the alpha 2-adrenoceptor. The interplay between opiates and alpha 2-adrenergic drugs in the acute secretion of growth hormone and prolactin, as well as the possible cross-tolerance between morphine (mu-opioid receptor agonist) and dexmedetomidine (alpha 2-adrenoceptor agonist) in growth hormone secretion were also evaluated. Dexmedetomidine dose-dependently increased plasma growth hormone and prolactin levels and decreased thyrotropin levels. The enhanced secretion of both growth hormone and prolactin was antagonized by atipamezole (an alpha 2-adrenoceptor antagonist) but not by prazosin (an alpha 1-adrenoceptor antagonist). Morphine (5 mg/kg)-induced stimulation of growth hormone secretion was antagonized by both naloxone (mu-opioid antagonist) and atipamezole. Naloxone, but not atipamezole, antagonized the morphine-induced increase in prolactin secretion. Dexmedetomidine increased growth hormone secretion in the saline pretreated rats, but did not do so in the morphine-tolerant rats. The stimulation of alpha 2-adrenoceptor enhances secretion of both growth hormone and prolactin. The adrenergic regulation of thyrotropin secretion still remains unclear. Evidently, adrenergic mechanisms are involved in the morphine-induced stimulation of growth hormone secretion, but not in the morphine-induced stimulation of prolactin secretion. In addition, there is a clear cross-tolerance between dexmedetomidine and morphine in growth hormone secretion of the rat.
Idänpään-Heikkilä
J J
JJ
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Rauhala
P
P
Männistö
P T
PT
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D013006:Growth Hormone / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D009020:Morphine / Q000494:pharmacology; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D011388:Prolactin / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013972:Thyrotropin / Q000187:drug effects / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D010908:Pituitary Hormones, Anterior; D017450:Receptors, Opioid, mu; D009020:Morphine; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone; D020926:Medetomidine