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Differential actions of AlF 4 and vanadate on canine trachealis muscle

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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 (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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References

  1. 1.

    Aaronson P, van Breemen C (1981) Effects of sodium gradient manipulation upon cellular calcium, Ca2+ fluxes and cellular sodium in the guinea-pig taenia coli. J Physiol (Lond) 319:443–461

  2. 2.

    Artemyev NO, Rarick HM, Mills JS, Skiba NP, Hamm HE (1992) Sites of interaction between Rod G-protein a-subunit and cGMP-phosphodiesterase c-subunit. J Biol Chem 267:25 067–25 072

  3. 3.

    Berridge MJ, Downes CP, Hanley MR (1982) Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 206:587–595

  4. 4.

    Blackmore PF, Bocckino SB, Waynick LE, Exton JH (1991) Role of guanine nucleotide-binding regulatory protein in the hydrolysis of hepatocyte phosphatidylinositol 4,5-bisphosphate by calcium-mobilizing hormones and the control of cell calcium. Studies utilizing aluminium fluoride. J Biol Chem 260:14 477–14 483

  5. 5.

    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

  6. 6.

    Brechler V, Pavoine C, Hanf R, Garbarz E, Fischmeister R, Pecker F (1992) Inhibition by glucagon of the cGMP-inhibited low Km cAMP-phosphodiesterase in heart is mediated by a pertussis-toxin-sensitive G protein. J Biol Chem 267:15 496–15 501

  7. 7.

    van Breemen C (1989) Cellular mechanisms regulating [Ca2+]i in smooth muscle. Annu Rev Physiol 51:315–329

  8. 8.

    Coburn RF, Baron CB (1990) Coupling mechanisms in airway muscle. Am J Physiol 258:L119-L133

  9. 9.

    Dominguez JH, Garcia JGN, Rothrock JK, English D, Mann C (1991) Fluoride mobilizes intracellular calcium and promotes Ca2+ influx in rat proximal tubules. Am J Physiol 261:F318-F327

  10. 10.

    Hall IP, Donaldnon J, Hill SJ (1990) Modulation of AlF 4 induced inositol phosphate formation by increases in tissue cyclic AMP content in bovine tracheal smooth muscle. Br J Pharmacol 100:646–650

  11. 11.

    Himpens B, Missiaen L, Droogmans G, Casteels R (1991) AlF 4 induces Ca2+ oscillations in guinea-pig ileal smooth muscle. Pflügers Arch 417:645–650

  12. 12.

    Hudgins PM, Bond GH (1981) Alterations by vanadate of contractility in vascular and intestinal smooth muscle preparations. Pharmacology 23:156–164

  13. 13.

    Inoue Y, Fishman PH, Rebois RV (1990) Differential activation of the stimulatory and inhibitory guanine nucleotide-binding proteins by fluoroaluminate in cells and in membranes. J Biol Chem 265:10 645–10 651

  14. 14.

    Jung JS, Hwang TH, Jung DK, Kim YK, Lee SH (1992) AlF 4 and vanadate stimulate chloride secretion in rabbit colon by a Ca2+-dependent mechanism. Pflügers Arch 420:515–521

  15. 15.

    Kahn RA (1991) Fluoride is not an activator of the smaller (20–25 kDa) GTP-binding proteins. J Biol Chem 266: 15 595–15 597

  16. 16.

    Krawietz W, Downs RW, Spiegel AM (1982) Vanadate stimulates adenylate cyclase via the guanine regulatory protein by a mechanism differing from that of fluoride. Biochem Pharmacol 31:843–848

  17. 17.

    Law SF, Yasuda K, Bell GI, Reisine T (1993) Gi alpha3 and G(o) alpha selectively associate with the cloned somatostatin receptor subtype SSTR2. J Biol Chem 268:10 721–10 727

  18. 18.

    Marc S, Leiber D, Harbon S (1988) Fluoroaluminate mimic muscarinic- and oxytocin-receptor-mediated generation of inositol phosphates and contraction in the intact guinea-pig myometrium. Role for a pertussis/cholera-toxin-insensitive G-protein. Biochem J 255:705–713

  19. 19.

    Mertz LM, Horn VJ, Baum BJ, Ambudkar IS (1990) Calcium entry in rat parotid acini: activation by carbachol and aluminium fluoride. Am J Physiol 258:C654-C661

  20. 20.

    Missiaen L, Wuytack F, De Smedt H, Vrolix M, Casteels R (1988) AlF 4 reversibly inhibits ‘P’-type cation transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase. Biochem J 253:827–833

  21. 21.

    Musk AW, Tees JG (1982) Asthma caused by occupational exposure to vanadium compounds. Med J Aust 1:183–184

  22. 22.

    Paris S, Pouyssegur J (1987) Further evidence for a phospholipase C-coupled G protein in Hamster fibroblasts. Induction of inositol phosphate formation by fluoroaluminate and vanadate and inhibition by pertussis toxin. J Biol Chem 262:1970–1976

  23. 23.

    Rasmussen H, Kelley G, Douglas JS (1990) Interaction between Ca and cAMP messenger system in regulation of airway smooth muscle contraction. Am J Physiol 258:L279-L288

  24. 24.

    Remaury A, Carrouy D, Daviaud D, Rouot B, Paris H (1993) Coupling of the alpha 2-adrenergic receptor to the inhibitory G-protein Gi and adenylate cyclase in HT 29 cells. Biochem J 292:283–288

  25. 25.

    Russel JA (1984) Differential inhibitory effect of isoproterenol on contractions of canine airways. J Appl Physiol 57:801–807

  26. 26.

    Simons TJB (1979) Vanadate — a new tool for biologists. Nature 281:337–338

  27. 27.

    Sternweis PC, Gilman AG (1982) Aluminium: a requirement for activation of the regulatory component of adenylate cyclase by fluoride. Proc Natl Acad Sci USA 99:4888–4891

  28. 28.

    Sternweis PC, Smrcka AV (1992) Regulation of phospholipase C by G proteins. Trends Biol Sci 17:502–506

  29. 29.

    Torphy TJ, Zeng C, Peterson SM, Fiscus RR, Rinard GA, Mayer SE (1985) Inhibitory effect of methacholine on drug-induced relaxation, cyclic AMP accumulation, and cyclic AMP-dependent protein kinase activation in canine tracheal smooth muscle. J Pharmacol Exp Ther 233:409–417

  30. 30.

    Torphy TJ, Zhou HL, Burman M, Huang LB (1991) Role of cyclic nucleotide phosphodiesterase isozymes in intact canine trachealis. Mol Pharmacol 39:376–384

  31. 31.

    Triggle DJ, Swamy VC (1980) Pharmacology of agents that affect calcium: agonists and antagonists. Chest 78:174–179

  32. 32.

    Ueda F, Karaki H, Urakawa N (1985) Contractile effects of vanadate on monkey and rabbit tracheal smooth muscle. Arch Int Pharmacodyn Ther 276:120–132

  33. 33.

    Zeng YY, Benishin CG, Pang PKT (1989) Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies with fluoride. J Pharmacol Exp Ther 250:343–351

  34. 34.

    Zhou HL, Torphy TJ (1991) Relationships between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators. J Pharmacol Exp Ther 258:972–978

  35. 35.

    Zhu J, Li W, Toews ML, Hexum TD (1992) Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase in bovine adrenal chromaffin cells in a pertussis-toxin-sensitive process. J Pharmacol Exp Ther 263:1479–1486

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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