The influence of indomethacin on the acth secretion induced by central stimulation of adrenergic receptors.
We had previously demonstrated that indomethacin affected the corticosterone secretion induced by central stimulation of alpha-but not beta-adrenergic receptors in conscious rats. In the present study we investigated whether hypothalamic and/or pituitary prostaglandins (PGs) were involved in the central adrenergic stimulation of ACTH secretion. Indomethacin, 2 mg/kg ip or 10 microg intracerebroventricularly (icv), was administered 15 min before phenylephrine (30 microg icv), an alpha-adrenergic agonist, clonidine (10 microg), an alpha2-adrenergic agonist, and isoprenaline (20 microg) or clenbuterol (10 microg), a beta1- or beta2-adrenergic agonist. One hour after the last injection the rats were decapitated and plasma levels of ACTH were measured. The present results show that the ACTH responses induced by icv administration of phenylephrine and clonidine were considerably impaired by icv or ip pretreatment with indomethacin, an inhibitor of prostaglandin synthesis. Indomethacin given by either route only slightly diminished the isoprenaline-induced ACTH response and did not substantially alter the clenbuterol-induced response. The adrenergic-induced ACTH responses were more potently inhibited by ip than by icv pretreatment with indomethacin, which may result from a stronger inhibition of PGs synthesis in the median eminence and anterior pituitary by ip pretreatment with indomethacin than in hypothalamic structures by its icv administration. These results indicate a significant involvement of PGs in central stimulation of the hypothalamic-pituitary adrenal (HPA) axis by alpha1- and alpha2- but not beta-adrenergic receptors.
Glód
R
R
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Cracow.
Gadek-Michalska
A
A
Bugajski
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002976:Clenbuterol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D010656:Phenylephrine; D000324:Adrenocorticotropic Hormone; D007545:Isoproterenol; D003000:Clonidine; D002976:Clenbuterol; D007213:Indomethacin