title: Gamma(2)-melanocyte-stimulating hormone suppression of systemic inflammatory responses to endotoxin is associated with modulation of central autonomic and neuroendocrine activities.
abstract: Central autonomic and neuroendocrine activities are important components of the host response to bacterial inflammation. We demonstrate that intravenous infusion of gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH), a potent autonomic regulating peptide, prevents lipopolysaccharide (LPS)-induced hypotension and tachycardia, and modulates the ACTH response to endotoxin. In the hypothalamic paraventricular nucleus, a major neuroendocrine and autonomic center, gamma(2)-MSH inhibits LPS-induced increases in CRF mRNA levels, but does not suppress LPS-augmented arginine vasopressin heteronuclear RNA expression. In the locus coeruleus, a brainstem noradrenergic center, gamma(2)-MSH inhibits LPS-induced increases in tyrosine hydroxylase mRNA levels. Gamma(2)-MSH inhibits LPS-induced IL-1beta gene expression in the brain, pituitary and thymus, and prevents increases in plasma NO levels. These findings reveal that gamma(2)-MSH attenuates systemic inflammatory responses to endotoxin and suggest that modulation of central autonomic and neuroendocrine activities by gamma(2)-MSH contributes to its anti-inflammatory effects.
authors.affiliation: Department of Cell Biology, Faculty of Medicine and Dentistry, and Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2H7.
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: J E
authors.initials: JE
authors.lastname: Wikberg
authors.forename: T L
authors.initials: TL
authors.lastname: Krukoff
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism; D019825:gamma-MSH / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019825:gamma-MSH; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase