title: Effect of histamine antagonists on myocardial carcinine metabolism during compound 48/80-induced shock.
abstract: Carcinine (beta-alanylhistamine) is an imidazole dipeptide that exists in mammalian hearts, increases cardiac contractility, and is metabolically linked to carnosine (beta-alanylhistidine), a non-mast cell histidine and histamine precursor during stress. We have previously shown that tissue carnosine levels are regulated by H1 and H2 receptors. This study evaluated the effects of H1, H2, and mast cell degranulation blockers on metabolism of carcinine and related imidazoles during shock induced by compound 48/80, a mast cell degranulator. Fifty 125-g male Sprague-Dawley rats were divided into nine ip treatment groups: saline, 48/80, lodoxamide (LOD, mast cell degranulation inhibitor), diphenhydramine (DPH, H1 antagonist), cimetidine (CIM, H2 antagonist), LOD + 48/80, CIM + 48/80, DPH + 48/80, or DPH + CIM + 48/80. Heart tissue was analyzed at 30 min by HPLC. 48/80 caused decreases in myocardial carnosine (P less than 0.01) and histidine (P less than 0.0001) levels and concomitant increases in carcinine (P less than 0.01), histamine (P less than 0.01), and 3-methylhistamine (P less than 0.05) compared to those of controls. These changes were inhibited by LOD or DPH. Treatment with CIM significantly increased myocardial carcinine levels compared to 48/80 alone (P less than 0.001) without an additional effect on the other compounds. These data indicate that carcinine is involved in the cardiac response to stress via the carnosine-histidine-histamine pathway. Compound 48/80-induced shock increases histamine metabolism via this pathway resulting in mobilization of myocardial carnosine and histidine to carcinine and histamine; this effect is increased by H2 receptor blockade.
authors.affiliation: Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick.
authors.forename: J C
authors.initials: JC
authors.lastname: Fitzpatrick
authors.forename: H
authors.initials: H
authors.lastname: Fisher
authors.forename: L
authors.initials: L
authors.lastname: Flancbaum
mesh_terms: D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology*; D006639:Histidine / Q000378:metabolism; D008297:Male; D008761:Methylhistamines / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D012769:Shock / Q000139:chemically induced / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine
chemical_list: D006633:Histamine Antagonists; D008761:Methylhistamines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D003189:p-Methoxy-N-methylphenethylamine; D006639:Histidine; C031205:3-methylhistamine; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D002336:Carnosine; D010072:Oxamic Acid; C021702:lodoxamide ethyl; C015055:carcinine