Differential actions of AlF4- and vanadate on canine trachealis muscle
Lee, S.H.; Hwang, T.H.; Jung, J.S.
Pflugers Archiv European Journal of Physiology 427(3-4): 295-300
1994
ISSN/ISBN: 0031-6768 PMID: 8072849 Document Number: 432261
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 (AlF-4-) 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 (Al-3+, 20 mu-M) and inhibited by deferoxamine (200 mu-M), a heavy metal chelator. Ca-2+ removal and 10 mu-M verapamil inhibited the contraction induced by AIF-4- and vanadate. AlF-4- and vanadate increased 45Ca influx in the absence and presence of verapamil. AlF-4--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 AlF-4- in forskolin-pretreated tissues. Vanadate increased inositol phosphate accumulation as did AlF-4-, although the magnitude of the increase was smaller than that produced by AlF-4-. The increases of inositol phosphate content by both drugs were not affected after the pretreatment by pertussis toxin. These results indicate that. in canine trachealis muscle, AlF-4- elicits contractions by Ca-2+ influx through potential-operated and -independent Ca-2+- channels and intracellular Ca-2+ release by inositol 1,4,5-triphosphate (InsP-3), which are mediated by stimulation of pertussis-toxin-insensitive G-proteins, and that the mechanisms of the vanadate-induced contraction is different from that of AlF-4-, although it may be partly explained by the stimulation of G-proteins.