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Differential actions of AlF 4 and vanadate on canine trachealis muscle

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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 (Al3+, 20 μM) and inhibited by deferoxamine (200 μM), a heavy metal chelator. Ca2+ removal and 10 μM verapamil inhibited the contraction induced by AlF 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 Ca2+ influx through potential-operated and -independent Ca2+ channels and intracellular Ca2+ 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.

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Correspondence to Sang Ho Lee.

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Lee, S.H., Hwang, T.H. & Jung, J.S. Differential actions of AlF 4 and vanadate on canine trachealis muscle. Pflügers Arch 427, 295–300 (1994). https://doi.org/10.1007/BF00374537

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Key words

  • Fluoroaluminate
  • Vanadate
  • G-protein
  • Trachealis muscle