Uncoupling of G-protein mediated fluoride contractions of vascular smooth muscle by pHi perturbations.
In the presence of extracellular Ca2+ (Cao), isolated preparations of rabbit aortas (RA) and epicardial porcine coronary arteries (PCA) contracted dose-dependently to the cumulative addition of NaF (2.5-12 mmol/l); the EC50 values were resp. 6.87 +/- 0.25 (n = 6) and 6.35 +/- 0.42 (n = 11) mmol/l. In Cao-free EGTA-containing solution, the vessel preparations were also contracted by NaF in the same concentration range; however, the maximum effect was only about 20-35% of the fluoride-induced contractions in Ca(2+)-containing solutions. Contractions induced in PCA by 10 mmol/l NaF in the presence and absence of Cao were unaffected by pretreatment with 0.5 mmol/l deferoxamine mesylate. These specific fluoride effects, not mimicked by other halogenides, seem to be only partly mediated by activation of G-protein; they were inhibited in 1.5 mmol/l Cao by verapamil and sodium nitroprusside (NaNP), in Ca(2+)-free solution only by NaNP. Slow developing and sustained contractions, similar in time course and amplitude to fluoride contractions, were induced in RA byy phorbol 12,13-dibutyrate. Contractions induced by depolarization (50 mmol/l KCl) and by NaF were additive, suggesting distinct mechanisms of action; NaF (2.5 and 10 mmol/l) shifted cumulative concentration-response (CCR) curves for PCA contractions to KCl (20-100 mmol/l) to the left and also potentiated the maximum response.(ABSTRACT TRUNCATED AT 250 WORDS)
Duong
H N
HN
Abteilung für Allgemeine Physiologie, Universität Ulm, Fed. Rep. of Germany.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
D009599:Nitroprusside; D015240:Phorbol 12,13-Dibutyrate; D014700:Verapamil; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D005459:Fluorides; D002118:Calcium