Influence of cyclooxygenase inhibitors on the central histaminergic stimulations of hypothalamic - pituitary - adrenal axis.
Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of different neurotransmitters involved in activation of HPA axis. In the present experiment we investigated whether endogenous prostaglandins are involved in the stimulation of ACTH and corticosterone secretion by histaminergic systems in the rat brain. Histamine (50 microg), histamine-trifluoromethyl-toluidine derivative (HTMT, 75microg) a selective and potent H(1)-receptor agonist, and amthamine (50 microg) a H(2)-receptor agonist given intracerebroventricularly (i.c.v.) to non-anesthetized rats considerably increased ACTH and corticosterone secretion 1h after administration. A non-selective cyclooxygenase inhibitor indomethacin (2 mg/kg i.p. or 10 microg i.c.v.), piroxicam (0.02 and 0.2 microg i.c.v.) a more potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (0.1 and 1.0 microg i.c.v.), a selective inhibitor of inducible cyclooxygenase (COX-2) were given 15 min before histamine and histamine receptor agonists. One hour after the last injection trunk blood from decapitated rats was collected for hormones determination. The histamine-induced ACTH and corticosterone secretion was significantly diminished by piroxicam and was not markedly altered by indomethacin and compound NS-398. The HTMT-elicited increase in ACTH and corticosterone secretion was significantly prevented by indomethacin and was not affected by piroxicam or compound NS-398. The amthamine-evoked increase in ACTH and corticosterone secretion was not markedly influenced by any cyclooxygenase blocker applied in the present experiment. These results indicate that the histamine H(1)-receptor transmitted central stimulation of the HPA axis is considerably mediated by prostaglandins generated by consititutive cyclooxygenase, whereas stimulation transmitted via H(2)-receptor does not significantly depend on endogenous prostaglandins mediation.
Bugajski
A J
AJ
Department of Pathophysiology, Jagiellonian University School of Medicine, Cracow, Poland.
Thor
P
P
Głód
R
R
Gadek-Michalska
A
A
Bugajski
J
J
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004334:Drug Administration Schedule; D006632:Histamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000502:physiology; D017442:Histamine Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D008297:Male; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000008:administration & dosage; D010894:Piroxicam / Q000008:administration & dosage / Q000493:pharmacokinetics; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017442:Histamine Agonists; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; D013844:Thiazoles; C087869:histamine trifluoromethyl-toluidide; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010894:Piroxicam; C076207:amthamine; D006632:Histamine; D000324:Adrenocorticotropic Hormone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D003345:Corticosterone; D007213:Indomethacin