Effect of indomethacin on the pituitary-adrenocortical response to adrenergic stimulation.
The role of prostaglandins (PGs) in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by adrenergic agonists and catecholamines was investigated in nonanesthetized rats. The cyclooxygenase and PGs synthesis inhibitor indomethacin was given systemically or intracerebroventricularly (icv) 15 min prior to phenylephrine (30 micrograms), clonidine (10 micrograms), and isoproterenol (20 micrograms), an alpha 1-, alpha 2-, and beta-adrenergic receptor agonists, respectively, or noradrenaline (10 micrograms) and adrenaline (10 micrograms). Indomethacin given ip (2 mg/kg) or icv (10 micrograms) almost abolished the increase in corticosterone secretion elicited by phenylephrine, considerably reduced the response to clonidine but did not markedly affect the response to isoproterenol. Pretreatment with indomethacin by either route strongly suppressed the corticosterone response to noradrenaline, but did not substantially affect the hormonal response to adrenaline. The above data indicate that prostaglandins considerably mediate the HPA axis response to central stimulation of alpha 1- and alpha 2-, but not beta-adrenergic receptors. They also point to significant involvement of prostaglandins in the noradrenaline-, but not adrenaline-induced HPA axis predominantly via alpha 1-and alpha 2-adrenergic receptors, whereas adrenaline exerts stimulation manly via beta-adrenergic receptors.
Bugajski
J
J
Department of Physiology, Polish Academy of Sciences, Cracow, Poland.
Gadek-Michalska
A
A
Borycz
J
J
Głód
R
R
Bugajski
A J
AJ
D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D018663:Adrenergic Agents; D016861:Cyclooxygenase Inhibitors; D010656:Phenylephrine; D007545:Isoproterenol; D003000:Clonidine; D003345:Corticosterone; D009638:Norepinephrine; D007213:Indomethacin; D004837:Epinephrine