The inhibitory effect of fluoride on carbachol-induced bovine bronchial contraction.
The effect of sodium fluoride (NaF) on the responsiveness of airway smooth muscle was investigated in bovine bronchial segments. NaF (0.5-10 mM) induced a delayed concentration-dependent active pressure (AP) and reduced the lactate concentration in the solution. Pyruvate (10 mM) increased the NaF-induced contraction. There was a 50 +/- 7% decrease in carbachol (10 microM)-induced AP when bronchi were pretreated with NaF (5 mM) and a 37 +/- 9% decrease when NaF (5 mM) was added during the maintained carbachol-induced contraction. These inhibitory effects were enhanced by KCN and hypoxia. When bronchi were pre-incubated with 10 microM verapamil, a calcium channel inhibitor, the contractile effect of 5 mM NaF was reduced to 8 +/- 3% of the control. PKC activity in bronchial smooth muscle was significantly increased by NaF (5 mM). Staurosporine (30 nM) abolished the contractile effect of NaF. These results suggest that: (1) NaF either contracts or relaxes bronchial smooth muscle depending on the experimental conditions; (2) the relaxing effect is related to the inhibitory action of NaF on glycolysis; (3) the contractile effect of NaF is possibly mediated by modulation of a calcium channel via a PKC-dependent pathway; (4) carbachol-induced contraction is glycolysis pathway dependent in the absence of NaF but switches to oxidative dependent in its presence.
Zhao
W
W
Laboratoire de Physiologie, Faculté de Victor Pachon, Université de Bordeaux 2, France.
Guénard
H
H
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology*
D002217:Carbachol; D012969:Sodium Fluoride