Histamine H2-receptor-mediated nitric oxide release from porcine endothelial cells.
The involvement of histamine-receptor subtypes in histamine-induced release of nitric oxide (NO) from porcine aortic endothelial cells was studied. NO release was measured directly by using an NO electrode and by electron paramagnetic resonance (EPR) spin trapping. NO release induced by histamine (200 microM) was reduced in the presence of 2 microM cimetidine, an H2-receptor antagonist, but not altered by 2 microM pyrilamine, an H1-receptor antagonist. Histamine-induced NO release was significantly reduced by the addition of 20 microM of the Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a membrane-permeable antagonist of cyclic adenosine monophosphate (cAMP). Application of 100 microM forskolin, an activator of adenylate cyclase, induced NO release from porcine aortic endothelial cells. Fura-2 acetoxymethylester (fura-2/AM) studies showed that addition of 100 microM histamine did not produce any significant increase in the use of free concentration of intracellular Ca2+. These results suggest that in porcine aortic endothelial cells, NO-mediated vasodilation might be caused by production of cAMP initiated through the histamine H2-receptor.
Second Department of Internal Medicine, University of Tokushima, Japan.
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Kishi
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Nakaya
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Ito
D000818:Animals; D001011:Aorta / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D011970:Receptors, Histamine H2; D009569:Nitric Oxide; D006632:Histamine; D000242:Cyclic AMP; D002118:Calcium