Differential actions of AlF 4 − and vanadate on canine trachealis muscle

Abstract

Fluoride (F-) a known stimulator of G-protein, has been reported to inhibit "P"-type ATPase activity in smooth muscles. On the other hand, vanadate, a strong "P"-type ATPase inhibitor, has been reported to stimulate G-protein in some cells. This study was designed to compare the contractile actions of fluoroaluminate (AlF4-) and vanadate and to clarify their mechanisms of actions by measuring changes in the amount of cyclic adenosine monophosphate (cAMP) and inositol phosphates. F- and vanadate induced strong contractions in canine trachealis muscle. The F(-)-induced contraction was potentiated by the addition of aluminum (Al3+, 20 microM) and inhibited by deferoxamine (200 microM), a heavy metal chelator. Ca2+ removal and 10 microM verapamil inhibited the contraction induced by AlF4- and vanadate. AlF4- and vanadate increased 45Ca influx in the absence and presence of verapamil. AlF4(-)-induced contractions were partially relaxed by isoproterenol (38.2 +/- 7.4%) in contrast with those induced by vanadate (72.1 +/- 5.3%), which could be explained by a decrease of tissue cAMP content by AlF4- in forskolin-pretreated tissues. Vanadate increased inositol phosphate accumulation as did AlF4-, although the magnitude of the increase was smaller than that produced by AlF4-. The increases of inositol phosphate content by both drugs were not affected after the pretreatment by pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)