Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Sep;119(2):213–222. doi: 10.1111/j.1476-5381.1996.tb15973.x

Some evidence against the involvement of arachidonic acid in muscarinic suppression of voltage-gated calcium channel current in guinea-pig ileal smooth muscle cells.

T Unno 1, S Komori 1, H Ohashi 1
PMCID: PMC1915857  PMID: 8886400

Abstract

1. To see if arachidonic acid (AA) plays a role in the sustained suppression of voltage-gated calcium channel currents produced by muscarinic receptor stimulation by carbachol (CCh), the effects of AA on membrane currents were examined in whole-cell voltage-clamped smooth muscle cells of the guinea-pig ileum. 2. In cells bathed in Ba2+ PSS and dialysed with Cs(+)-based low EGTA (0.05 mM) pipette solution, and in which Ba2+ current (IBa) flowing through voltage-gated calcium channels was evoked repeatedly by stepping to 0 mV from the holding potential of -60 mV, AA (1-30 microM), applied extracellularly, gradually suppressed IBa in a concentration-dependent manner. The IBa suppression was observed even with 20 mM EGTA in the pipette. 3. AA (3 microM) and CCh (10 microM) shifted the voltage-dependent inactivation curve of IBa in the negative potential direction, but the effect of AA differed from that of CCh in that an accompanying appreciable decrease in the slope was observed. 4. The sustained suppression of IBa induced by CCh (10 microM) remained almost unaltered after pretreatment with 4-bromophenacyl bromide (10 microM), an inhibitor of phospholipase A2, or a combination of indomethacin (10 microM), an inhibitor of the cyclo-oxygenase pathway, and nordihydroguaiaretic acid (10 microM), an inhibitor of the lipoxygenase pathway. 5. In cells bathed in Ca2+ PSS and dialysed with K(+)-based pCa 6.5 pipette solution, voltage-dependent Ca2+ current (ICa) and K+ current (IK) were recorded simultaneously. AA (3 microM) suppressed IK as well as ICa, whereas CCh (10 microM) suppressed ICa but not IK. 6. We conclude from these results that AA or its metabolite is unlikely to be involved in the sustained suppression of voltage-gated calcium channel current induced by muscarinic receptor stimulation in guinea-pig ileal smooth muscle cells.

Full text

PDF
213

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Axelrod J. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans. 1990 Aug;18(4):503–507. doi: 10.1042/bst0180503. [DOI] [PubMed] [Google Scholar]
  2. Beech D. J., Bernheim L., Hille B. Pertussis toxin and voltage dependence distinguish multiple pathways modulating calcium channels of rat sympathetic neurons. Neuron. 1992 Jan;8(1):97–106. doi: 10.1016/0896-6273(92)90111-p. [DOI] [PubMed] [Google Scholar]
  3. Benham C. D., Bolton T. B., Lang R. J. Acetylcholine activates an inward current in single mammalian smooth muscle cells. Nature. 1985 Jul 25;316(6026):345–347. doi: 10.1038/316345a0. [DOI] [PubMed] [Google Scholar]
  4. Bernheim L., Beech D. J., Hille B. A diffusible second messenger mediates one of the pathways coupling receptors to calcium channels in rat sympathetic neurons. Neuron. 1991 Jun;6(6):859–867. doi: 10.1016/0896-6273(91)90226-p. [DOI] [PubMed] [Google Scholar]
  5. Bolton T. B., Lim S. P. Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine. J Physiol. 1989 Feb;409:385–401. doi: 10.1113/jphysiol.1989.sp017504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bolton T. B. The depolarizing action of acetylcholine or carbachol in intestinal smooth muscle. J Physiol. 1972 Feb;220(3):647–671. doi: 10.1113/jphysiol.1972.sp009728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Droogmans G., Callewaert G. Ca2+-channel current and its modification by the dihydropyridine agonist BAY k 8644 in isolated smooth muscle cells. Pflugers Arch. 1986 Mar;406(3):259–265. doi: 10.1007/BF00640911. [DOI] [PubMed] [Google Scholar]
  8. Gong M. C., Kinter M. T., Somlyo A. V., Somlyo A. P. Arachidonic acid and diacylglycerol release associated with inhibition of myosin light chain dephosphorylation in rabbit smooth muscle. J Physiol. 1995 Jul 1;486(Pt 1):113–122. doi: 10.1113/jphysiol.1995.sp020795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graber R., Sumida C., Nunez E. A. Fatty acids and cell signal transduction. J Lipid Mediat Cell Signal. 1994 Mar;9(2):91–116. [PubMed] [Google Scholar]
  10. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  11. Hayes J. S., Brunton L. L. Functional compartments in cyclic nucleotide action. J Cyclic Nucleotide Res. 1982;8(1):1–16. [PubMed] [Google Scholar]
  12. Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977 Apr;69(4):497–515. doi: 10.1085/jgp.69.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Inoue R. Effect of external Cd2+ and other divalent cations on carbachol-activated non-selective cation channels in guinea-pig ileum. J Physiol. 1991 Oct;442:447–463. doi: 10.1113/jphysiol.1991.sp018802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Inoue R., Isenberg G. Effect of membrane potential on acetylcholine-induced inward current in guinea-pig ileum. J Physiol. 1990 May;424:57–71. doi: 10.1113/jphysiol.1990.sp018055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Inoue R., Kitamura K., Kuriyama H. Acetylcholine activates single sodium channels in smooth muscle cells. Pflugers Arch. 1987 Sep;410(1-2):69–74. doi: 10.1007/BF00581898. [DOI] [PubMed] [Google Scholar]
  16. Ito Y., Kozawa O., Tokuda H., Kotoyori J., Oiso Y. Vasopressin induces arachidonic acid release through pertussis toxin-sensitive GTP-binding protein in aortic smooth muscle cells: independence from phosphoinositide hydrolysis. J Cell Biochem. 1993 Oct;53(2):169–175. doi: 10.1002/jcb.240530210. [DOI] [PubMed] [Google Scholar]
  17. Kirber M. T., Ordway R. W., Clapp L. H., Walsh J. V., Jr, Singer J. J. Both membrane stretch and fatty acids directly activate large conductance Ca(2+)-activated K+ channels in vascular smooth muscle cells. FEBS Lett. 1992 Feb 3;297(1-2):24–28. doi: 10.1016/0014-5793(92)80319-c. [DOI] [PubMed] [Google Scholar]
  18. Komori S., Bolton T. B. Calcium release induced by inositol 1,4,5-trisphosphate in single rabbit intestinal smooth muscle cells. J Physiol. 1991 Feb;433:495–517. doi: 10.1113/jphysiol.1991.sp018440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Komori S., Bolton T. B. Role of G-proteins in muscarinic receptor inward and outward currents in rabbit jejunal smooth muscle. J Physiol. 1990 Aug;427:395–419. doi: 10.1113/jphysiol.1990.sp018178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Komori S., Kawai M., Takewaki T., Ohashi H. GTP-binding protein involvement in membrane currents evoked by carbachol and histamine in guinea-pig ileal muscle. J Physiol. 1992 May;450:105–126. doi: 10.1113/jphysiol.1992.sp019118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kramer R. M. Structure, function and regulation of mammalian phospholipases A2. Adv Second Messenger Phosphoprotein Res. 1993;28:81–89. [PubMed] [Google Scholar]
  22. Kurachi Y., Ito H., Sugimoto T., Shimizu T., Miki I., Ui M. Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel. Nature. 1989 Feb 9;337(6207):555–557. doi: 10.1038/337555a0. [DOI] [PubMed] [Google Scholar]
  23. Lazarowski E. R., Boucher R. C., Harden T. K. Calcium-dependent release of arachidonic acid in response to purinergic receptor activation in airway epithelium. Am J Physiol. 1994 Feb;266(2 Pt 1):C406–C415. doi: 10.1152/ajpcell.1994.266.2.C406. [DOI] [PubMed] [Google Scholar]
  24. Matarese V., Stone R. L., Waggoner D. W., Bernlohr D. A. Intracellular fatty acid trafficking and the role of cytosolic lipid binding proteins. Prog Lipid Res. 1989;28(4):245–272. doi: 10.1016/0163-7827(89)90001-5. [DOI] [PubMed] [Google Scholar]
  25. McDonald T. F., Pelzer S., Trautwein W., Pelzer D. J. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev. 1994 Apr;74(2):365–507. doi: 10.1152/physrev.1994.74.2.365. [DOI] [PubMed] [Google Scholar]
  26. Meves H. Modulation of ion channels by arachidonic acid. Prog Neurobiol. 1994 Jun;43(2):175–186. doi: 10.1016/0301-0082(94)90012-4. [DOI] [PubMed] [Google Scholar]
  27. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992 Oct 23;258(5082):607–614. doi: 10.1126/science.1411571. [DOI] [PubMed] [Google Scholar]
  28. Ohya Y., Terada K., Kitamura K., Kuriyama H. Membrane currents recorded from a fragment of rabbit intestinal smooth muscle cell. Am J Physiol. 1986 Sep;251(3 Pt 1):C335–C346. doi: 10.1152/ajpcell.1986.251.3.C335. [DOI] [PubMed] [Google Scholar]
  29. Pacaud P., Bolton T. B. Relation between muscarinic receptor cationic current and internal calcium in guinea-pig jejunal smooth muscle cells. J Physiol. 1991 Sep;441:477–499. doi: 10.1113/jphysiol.1991.sp018763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Piomelli D., Volterra A., Dale N., Siegelbaum S. A., Kandel E. R., Schwartz J. H., Belardetti F. Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition of Aplysia sensory cells. Nature. 1987 Jul 2;328(6125):38–43. doi: 10.1038/328038a0. [DOI] [PubMed] [Google Scholar]
  31. Shimada T., Somlyo A. P. Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. J Gen Physiol. 1992 Jul;100(1):27–44. doi: 10.1085/jgp.100.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Starmer C. F., Nesterenko V. V., Gilliam F. R., Grant A. O. Use of ionic currents to identify and estimate parameters in models of channel blockade. Am J Physiol. 1990 Aug;259(2 Pt 2):H626–H634. doi: 10.1152/ajpheart.1990.259.2.H626. [DOI] [PubMed] [Google Scholar]
  33. Tsien R. Y. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry. 1980 May 27;19(11):2396–2404. doi: 10.1021/bi00552a018. [DOI] [PubMed] [Google Scholar]
  34. Unno T., Komori S., Ohashi H. Inhibitory effect of muscarinic receptor activation on Ca2+ channel current in smooth muscle cells of guinea-pig ileum. J Physiol. 1995 May 1;484(Pt 3):567–581. doi: 10.1113/jphysiol.1995.sp020687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wang X. B., Osugi T., Uchida S. Muscarinic receptors stimulate Ca2+ influx via phospholipase A2 pathway in ileal smooth muscles. Biochem Biophys Res Commun. 1993 Jun 15;193(2):483–489. doi: 10.1006/bbrc.1993.1649. [DOI] [PubMed] [Google Scholar]
  36. Yanagisawa T., Ishii K., Hashimoto H., Taira N. Differential coupling to positive inotropic responses of cyclic AMP produced by stimulation of beta 1- and beta 2-adrenergic receptors. J Cardiovasc Pharmacol. 1989 Jan;13(1):64–75. [PubMed] [Google Scholar]
  37. Yousufzai S. Y., Abdel-Latif A. A. Involvement of a pertussis toxin-sensitive G protein-coupled phospholipase A2 in agonist-stimulated arachidonic acid release in membranes isolated from bovine iris sphincter smooth muscle. Membr Biochem. 1993 Jan-Mar;10(1):29–42. doi: 10.3109/09687689309150250. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES