title: Role of prostaglandins and nitric oxide in the lipopolysaccharide-induced ACTH and corticosterone response.
abstract: This study was designed to determine the role of endogenous prostaglandins (PG) and nitric oxide (NO) in the lipopolysaccharide (LPS)-induced ACTH and corticosterone secretion in conscious rats. LPS (0.5 and 1 mg/kg) given i.p. stimulated the hypothalamic-pituitary-adrenocortical (HPA) activity measured 2 h later. A non-selective cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.), piroxicam (2 mg/kg i.p.), a more potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (2 mg/kg i.p.), a selective inhibitor of inducible cyclooxygenase (COX-2) given 30 min before LPS (1 mg/kg i.p.) significantly diminished both the LPS-induced ACTH and corticosterone secretion. COX-2 blocker was the most potent inhibitor of ACTH secretion (72.3%). Nomega-nitro-L-arginine methyl ester (L-NAME 2 and 10 mg/kg i.p.), a non-selective nitric oxide synthase (NOS) blocker given 15 min before LPS did not substantially alter plasma ACTH and corticosterone levels 2 h later. Aminoguanidine (AG 100 mg/kg i.p.), a selective inducible nitric oxide synthase (iNOS) inhibitor, considerably enhanced ACTH and corticosterone secretion induced by a lower dose (0.5 mg/kg) of LPS and did not significantly alter this secretion after a larger dose (1 mg/kg) of LPS. L-NAME did not markedly affect the indomethacin-induced inhibition of ACTH and corticosterone response. By contrast, aminoguanidine abolished the indomethacin-induced reduction of ACTH and corticosterone secretion after LPS. These results indicate an opposite action of PG generated by cyclooxygenase and NO synthesized by iNOS in the LPS-induced HPA-response.
authors.affiliation: Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Gadek-Michalska
authors.forename: J
authors.initials: J
authors.lastname: Bugajski
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009578:Nitrobenzenes / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010894:Piroxicam; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone; D007213:Indomethacin