FLUORIDE IS A CONTRACTILE AGENT OF GUINEA-PIG AIRWAY SMOOTH-MUSCLE

1. Guinea pig parenchymal lung strips and tracheal smooth muscle contract potently after NaF-addition. Maximal contractions of lung strips and tracheal rings induced by NaF were 208 +/- 17% (n = 6) and 151 +/- 8% (n = 4) of the maximal histamine response respectively. 2. The -log EC50-value for NaF on lung strips and tracheal rings was 2.38 +/- 0.01 (n = 6) and 2.28 +/- 0.01 (n = 4) respectively. 3. Contractions induced by NaF were augmented after Al3+ pretreatment, suggesting the involvement of a G-protein. NaF responses were not affected by blockade of H-1-, muscarinic-, leukotriene C4- or leukotriene D4-receptors, indicating that mast cell degranulation or nerve activation is most probably not implicated. 4. Contractions after NaF-addition were relatively insensitive to removal of extracellular calcium and were reversed via cAMP- and cGMP-mediated pathways. 5. Relaxation studies with (-)isoprenaline and 8-bromo-cGMP on lung strips, precontracted to similar levels with either a H-1-agonist, KCl or NaF, showed that the level of relaxation depends on the contractile agent that is used. 6. After precontraction with KCl (-)isoprenaline relaxes lung strips only to 58 +/- 9% (n = 5) of the initial contraction, whereas lung strips precontracted with NaF or a H-1-agonist relax 114 +/- 8% (n = 4) and 120 +/- 7% (n = 5) respectively with (-)isoprenaline. 7. Similar results were obtained with relaxation induced with 8-bromo-cGMP. 8. These findings suggest that NaF-induced contractions are elicited via a mechanism, that is probably similar to that of the H-1-receptor. The involvement of a G-protein in the observed NaF-responses is therefore likely.