ATP-sensitive K+ channels mediate regulation of substance P release via the prejunctional histamine H3 receptor

Eur J Pharmacol. 1995 Apr 13;277(1):45-9. doi: 10.1016/0014-2999(95)00057-r.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Analysis of Variance
  • Animals
  • Benzopyrans / administration & dosage
  • Benzopyrans / pharmacology
  • Cromakalim
  • Glyburide / administration & dosage
  • Glyburide / pharmacology
  • Hindlimb
  • Histamine Agonists / administration & dosage
  • Histamine Agonists / pharmacology
  • Injections, Intravenous
  • Male
  • Methylhistamines / administration & dosage
  • Methylhistamines / pharmacology
  • Neuromuscular Junction / drug effects
  • Potassium Channel Blockers
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H3 / drug effects
  • Receptors, Histamine H3 / metabolism*
  • Skin / drug effects
  • Skin / metabolism
  • Stereoisomerism
  • Substance P / metabolism*
  • Tetraethylammonium
  • Tetraethylammonium Compounds / administration & dosage
  • Tetraethylammonium Compounds / pharmacology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology

Substances

  • Benzopyrans
  • Histamine Agonists
  • Methylhistamines
  • Potassium Channel Blockers
  • Potassium Channels
  • Pyrroles
  • Receptors, Histamine H3
  • Tetraethylammonium Compounds
  • Vasodilator Agents
  • Cromakalim
  • Substance P
  • Tetraethylammonium
  • alpha-methylhistamine
  • Adenosine Triphosphate
  • Glyburide