Document Detail

Effect of histamine antagonists on myocardial carcinine metabolism during compound 48/80-induced shock.
MedLine Citation:
PMID:  2214737     Owner:  NLM     Status:  MEDLINE    
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.
J C Fitzpatrick; H Fisher; L Flancbaum
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of surgical research     Volume:  49     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1990 Oct 
Date Detail:
Created Date:  1990-11-16     Completed Date:  1990-11-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  293-7     Citation Subset:  IM    
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick.
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MeSH Terms
Carnosine / analogs & derivatives*,  metabolism
Chromatography, High Pressure Liquid
Cimetidine / pharmacology
Diphenhydramine / pharmacology
Histamine / metabolism
Histamine Antagonists / pharmacology*
Histidine / metabolism
Methylhistamines / metabolism
Myocardium / metabolism*
Oxamic Acid / analogs & derivatives,  pharmacology
Rats, Inbred Strains
Receptors, Histamine H1 / physiology
Receptors, Histamine H2 / physiology
Shock / chemically induced,  metabolism*
Reg. No./Substance:
0/Histamine Antagonists; 0/Methylhistamines; 0/Receptors, Histamine H1; 0/Receptors, Histamine H2; 305-84-0/Carnosine; 4091-50-3/p-Methoxy-N-methylphenethylamine; 471-47-6/Oxamic Acid; 51-45-6/Histamine; 51481-61-9/Cimetidine; 53882-13-6/lodoxamide ethyl; 56897-53-1/carcinine; 58-73-1/Diphenhydramine; 644-42-8/3-methylhistamine; 71-00-1/Histidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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