THE INHIBITORY EFFECT OF FLUORIDE ON CARBACHOL-INDUCED BOVINE BRONCHIAL CONTRACTION

The effect of sodium fluoride (NaF) on the responsiveness of airway sm ooth muscle was investigated in bovine bronchial segments. NaF (0.5-10 mM) induced a delayed concentration-dependent active pressure (AP) an d reduced the lactate concentration in the solution. Pyruvate (10 mM) increased the NaF-induced contraction. There was a 50 +/- 7% decrease in carbachol (10 mu M)-induced AP when bronchi were pretreated with Na F (5 mM) and a 37 +/- 9% decrease when NaF (5 mM) was added during the maintained carbachol-induced contraction. These inhibitory effects we re enhanced by KCN and hypoxia. When bronchi were pre-incubated with 1 0 mu M verapamil, a calcium channel inhibitor, the contractile effect of 5 mM NaF was reduced to 8 +/- 3% of the control. PKC activity in br onchial smooth muscle was significantly increased by NaF (5 mM). Staur osporine (30 nM) abolished the contractile effect of NaF. These result s suggest that: (1) NaF either contracts or relaxes bronchial smooth m uscle depending on the experimental conditions; (2) the relaxing effec t is related to the inhibitory action of NaF on glycolysis; (3) the co ntractile effect of NaF is possibly mediated by modulation of a calciu m channel via a PKC-dependent pathway; (4) carbachol-induced contracti on is glycolysis pathway dependent in the absence of NaF but snitches to oxidative dependent in its presence. (C) 1997 Elsevier Science B.V.