A potassium channel activator modulates both excitatory noncholinergic and cholinergic neurotransmission in guinea pig airways.
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 iv.) and propranolol (1 mg/kg iv.), 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 micrograms/kg i.v. (P less than .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 iv.), an inhibitor of ATP-sensitive potassium channels, blocked its effect. Cromakalim had no inhibitory effect on exogenous substance P (5-25 micrograms/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 vagalcholinergic and exogenous acetylcholine (0.3-2 micrograms/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.
Ichinose
M
M
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Barnes
P J
PJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D019806:Cromakalim; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects*
D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D002211:Capsaicin; D005905:Glyburide; D010646:Phentolamine