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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1995-7-24
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pubmed:abstractText |
Norepinephrine release contributes to ischemic cardiac dysfunction and arrhythmias. Because activation of histamine H3-receptors inhibits norepinephrine release, we searched for the presence of H3-receptors directly in sympathetic nerve endings (cardiac synaptosomes) isolated from surgical specimens of human atria. Norepinephrine was released by depolarization with K+. The presence of H3-receptors was ascertained because the selective H3-receptor agonists (R) alpha-methylhistamine and imetit reduced norepinephrine release, and the specific H3-receptor antagonist thioperamide blocked this effect. Norepinephrine release was exocytotic, since it was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220. Functional relevance of these H3-receptors was obtained by showing that transmural electrical stimulation of sympathetic nerve endings in human atrial tissue increased contractility, an effect blocked by propranolol and attenuated in a concentration-dependent manner by (R) alpha-methylhistamine. Also, thioperamide antagonized the effect of (R) alpha-methylhistamine. Our findings are the first demonstration that H3-receptors are present in sympathetic nerve endings in the human heart, where they modulate adrenergic responses by inhibiting norepinephrine release. Since myocardial ischemia causes intracardiac histamine release, H3-receptor-induced attenuation of sympathetic neurotransmission may be clinically relevant.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Histamine Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Methylhistamines,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Histamine H3,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 31-8220,
http://linkedlifedata.com/resource/pubmed/chemical/Thiourea,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-methylhistamine,
http://linkedlifedata.com/resource/pubmed/chemical/imetit,
http://linkedlifedata.com/resource/pubmed/chemical/thioperamide
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0009-7330
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
77
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
206-10
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7788879-Cell Separation,
pubmed-meshheading:7788879-Electric Stimulation,
pubmed-meshheading:7788879-Exocytosis,
pubmed-meshheading:7788879-Heart,
pubmed-meshheading:7788879-Histamine Agonists,
pubmed-meshheading:7788879-Histamine Antagonists,
pubmed-meshheading:7788879-Humans,
pubmed-meshheading:7788879-Imidazoles,
pubmed-meshheading:7788879-Indoles,
pubmed-meshheading:7788879-Methylhistamines,
pubmed-meshheading:7788879-Myocardial Ischemia,
pubmed-meshheading:7788879-Myocardium,
pubmed-meshheading:7788879-Norepinephrine,
pubmed-meshheading:7788879-Piperidines,
pubmed-meshheading:7788879-Protein Kinase C,
pubmed-meshheading:7788879-Receptors, Histamine H3,
pubmed-meshheading:7788879-Synaptosomes,
pubmed-meshheading:7788879-Thiourea
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pubmed:year |
1995
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pubmed:articleTitle |
Functional identification of histamine H3-receptors in the human heart.
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pubmed:affiliation |
Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, U.S. Gov't, P.H.S.
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