Abstract
Perfusion of histamine (10(-3) M) elicited a significant increase of immunoreactive substance P release in the subcutaneous perfusate in the rat hindpaw. The active L-enantiomer of cromakalim, lemakalim (50 micrograms/kg, i.v.), a selective K+ channel activator, significantly inhibited the immunoreactive substance P release. Glibenclamide (10 mg/kg, i.v.), an ATP-sensitive K+ channel blocker, abolished the response to lemakalim on the release of immunoreactive substance P. R(-)-alpha-methylhistamine (1 mg/kg, i.v.), a specific histamine H3 receptor agonist, significantly inhibited the release of immunoreactive substance P. Glibenclamide (10 mg/kg, i.v.) antagonized the inhibitory effect of R(-)-alpha-methylhistamine. Tetraethylammonium (10 mg/kg, i.p.), a K+ channel blocker, also reduced the inhibitory effect significantly. These results suggest that the inhibition of substance P release from sensory nerve endings via prejunctional histamine H3 receptors may be achieved by activating the ATP-sensitive K+ channel coupled to the histamine H3 receptor in the rat skin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / pharmacology
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Analysis of Variance
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Animals
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Benzopyrans / administration & dosage
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Benzopyrans / pharmacology
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Cromakalim
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Glyburide / administration & dosage
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Glyburide / pharmacology
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Hindlimb
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Histamine Agonists / administration & dosage
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Histamine Agonists / pharmacology
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Injections, Intravenous
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Male
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Methylhistamines / administration & dosage
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Methylhistamines / pharmacology
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Neuromuscular Junction / drug effects
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Potassium Channel Blockers
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Potassium Channels / drug effects
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Potassium Channels / metabolism*
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Pyrroles / administration & dosage
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Pyrroles / pharmacology
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Radioimmunoassay
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Rats
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Rats, Wistar
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Receptors, Histamine H3 / drug effects
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Receptors, Histamine H3 / metabolism*
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Skin / drug effects
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Skin / metabolism
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Stereoisomerism
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Substance P / metabolism*
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Tetraethylammonium
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Tetraethylammonium Compounds / administration & dosage
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Tetraethylammonium Compounds / pharmacology
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Vasodilator Agents / administration & dosage
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Vasodilator Agents / pharmacology
Substances
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Benzopyrans
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Histamine Agonists
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Methylhistamines
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Potassium Channel Blockers
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Potassium Channels
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Pyrroles
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Receptors, Histamine H3
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Tetraethylammonium Compounds
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Vasodilator Agents
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Cromakalim
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Substance P
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Tetraethylammonium
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alpha-methylhistamine
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Adenosine Triphosphate
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Glyburide