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Functional identification of histamine H3-receptors in the human heart.
- Source :
-
Circulation research [Circ Res] 1995 Jul; Vol. 77 (1), pp. 206-10. - Publication Year :
- 1995
-
Abstract
- 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.
- Subjects :
- Cell Separation
Electric Stimulation
Exocytosis
Histamine Agonists pharmacology
Histamine Antagonists
Humans
Imidazoles pharmacology
In Vitro Techniques
Indoles pharmacology
Methylhistamines pharmacology
Myocardial Ischemia physiopathology
Norepinephrine metabolism
Piperidines pharmacology
Protein Kinase C antagonists & inhibitors
Receptors, Histamine H3 drug effects
Synaptosomes metabolism
Thiourea analogs & derivatives
Thiourea pharmacology
Heart physiology
Myocardium chemistry
Receptors, Histamine H3 analysis
Receptors, Histamine H3 physiology
Synaptosomes chemistry
Synaptosomes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0009-7330
- Volume :
- 77
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 7788879
- Full Text :
- https://doi.org/10.1161/01.res.77.1.206