A potassium channel activator modulates both excitatory noncholinergic and cholinergic neurotransmission in guinea pig airways

M. Ichinose, P. J. Barnes

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

The effect of a potassium channel activator, cromakalim (BRL 34915), on excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic neural bronchoconstriction was studied in guinea pigs. We monitored airway opening pressure as an index of airway caliber. After atropine (1 mg/kg i.v.) and propranolol (1 mg/kg i.v.), bilateral vagal stimulation evoked an e-NANC response. Cromakalim did not alter basal airway caliber, but reduced the e-NANC response to vagal stimulation in a dose-dependent manner, with a maximal inhibition of 71.9 ± 9.2% (mean ± S.E.) at 400 μg/kg i.v. (P < .01). Pretreatment with phentolamine (2.5 mg/kg i.v.) had no effect on the inhibitory response produced by cromakalim but glibenclamide (25 mg/kg i.v.), an inhibitor of ATP-sensitive potassium channels, blocked its effect. Cromakalim had no inhibitory effect on exogenous substance P (5-25 μg/kg i.v.)-induced bronchoconstriction. In animals depleted of tachykinins by capsaicin (50 mg/kg s.c.) pretreatment, cromakalim had an inhibitory effect on both vagal-cholinergic and exogenous acetylcholine (0.3-2 μg/kg i.v.)-induced bronchoconstriction, although the inhibitory effect was significantly greater on neural stimulation. We conclude that potassium channels modulate both e-NANC and cholinergic neurotransmission, and to a lesser extent acetylcholine-induced bronchoconstriction in guinea pig airways.

Original languageEnglish
Pages (from-to)1207-1212
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume252
Issue number3
Publication statusPublished - 1990 Apr 27
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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