ATP-sensitive K+ channels mediate regulation of substance P release via the prejunctional histamine H3 receptor.
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.
Ohkubo
T
T
Department of Pharmacology, Fukuoka Dental College, Japan.
Shibata
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006614:Hindlimb; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008761:Methylhistamines / Q000008:administration & dosage / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013373:Substance P / Q000378:metabolism*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D001578:Benzopyrans; D017442:Histamine Agonists; D008761:Methylhistamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D018100:Receptors, Histamine H3; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D013373:Substance P; D019789:Tetraethylammonium; C069357:alpha-methylhistamine; D000255:Adenosine Triphosphate; D005905:Glyburide