Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
권호 표지

Arachidonic Acid Ingibits Norepinephrine Release through Blocking of Voltage-sensitive $Ca^{2+}$ Channels in PC12 Cells

  • Choi, Se-Young (Department of Life Science and Basic Science Research Institute, Pohang University of Science and Technology) ;
  • Park, Tae-Ju (Department of Life Science and Basic Science Research Institute, Pohang University of Science and Technology) ;
  • Choi, Jun-Ho (Department of Life Science and Basic Science Research Institute, Pohang University of Science and Technology) ;
  • Kim, Kyong-Tai (Department of Life Science and Basic Science Research Institute, Pohang University of Science and Technology)
  • Published : 1997.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

We studied the mechanism of arachidonic acid on the secretion of a neurotransmitter in rat pheochromocytoma PC12 cells. Arachidonic acid inhibited the 70 mM $K^+$-induced secretion of norepinephrine. Arachidonic acid also inhibited the 70 mM $K^+$-induced $Ca^{2+}$ mobilization which is due to the opening of the voltage-sensitive $Ca^{2+}$ channels (VSCC). Both the half maximal inhibitory concentration ($IC_{50}$) of the norepinephrine secretion and VSCC coincided at 30 uM. The major oxidized metabolites of arachidonic acid, prostaglandins did not mimic the inhibitory effect of arachidonic acid. Nordihydroguaiaretic acid (NDGA) and indomethacin which are inhibitors of lipoxygenase and cyclooxygenase, respectively, did not block the inhibitory effect of arachidonic acid. The results suggest that arachidonic acid serves as a signal itself, not in the form of metabolites. The pretreatment of various $K^+$ channel blockers such as 4-aminopyridine, tetraethylarnmonium, glipizide, or glibenclamide also did not show any effect on the inhibitory effect of arachidonic acid. Through these results we suggest that arachidonic acid regulates VSCC directly and affects the secretion of neurotransmitters.

Keywords

References

  1. Proc Natl Acad Sci USA v.87 Fatty acid inhibits apical membrance chloride channels in airway epithelia Anderson MP;Welsh KJ
  2. J Biol Chem v.266 Lipid activation of protein kinase C Bell RM;Burns DJ
  3. Trend Biochem Sci v.15 The control of free arachidonic acid levels Burgoyne RD;Morgan A
  4. Br J Pharmacol v.118 characterization of $Na^{+}$influx mediated by $ATP^{4-} -activated $P_2purinoceptor in PC12 cells Choi SY;Kim KT
  5. Neurochem Res v.18 Involvement of phospholipase $A_2$and arachidonic acid in the depolarization-evoked accumulation of $Ca^{2+}$ in huppocampal mossy fiber nerve endings Damron DS;Dorman RV
  6. J Biol Chem v.268 Arachidodonic acid and endothelin potentiate$ Ca^{2+}transient in rat cardiac myocytes via inhibition of distinct $K^{+}$channels Damron DS;Van Wagoner DR;Moravec CS;Bond M
  7. Circ Res v.72 Modulation of $Ca^{2+}$cycling in cardiac myocytes by arachidonic acid Damron DS;Bond M
  8. J Biol Chem v.269 Arachidonic acid increases c-fos and Egr-1 mRNA in 3T3 fibroblasts by formation of prostaglandin$E_2$ and activation of protein kinase C Danesch U;Weber PC;Sellmayer A
  9. Am J Physiol v.235 Simultaneous analysis of families of sigmoidal curves;application to bioassay, radioligand assay, and physiological dose-response curves De Lean A;Munson PJ;Rodbard D
  10. Neuron v.11 Arachidonic acid inhibits sodium currents and synaptic transmittion in cultured striatal neurons Fraser DD;Hoehn K;Weiss S;MacVicar BA
  11. J Biol Chem v.260 A new generation of $Ca^{2+}$indicators with greatly improved fluorescence properties Grynkiewicz G;Poenie M;Tsien RY
  12. Science v.252 Regulation of Ras-GAP and the neurofibromatosis-a gene product by eicosanoids Han JW;McCormick F;Macara IG
  13. Proc Natl Acad Sci USA v.91 External blockade of the major cardiac delayedrectifier $R^{+}$channel (Kv1.5)by polyunsaturated fatty acids Honore E;Barhanin J;Attali B;Lesage F;Lazdunski M
  14. Proc Natl Acad Sci v.89 Long-chain fatty acids activate calcium channels in ventricular myocytes Huang JMC;Xian H;Bacaner M
  15. Proc Natl Acad Sci USA v.87 Direct modulation of secretory chloride channels by arachidonic acid and other cis-unsaturated fatty acids Hwang TC;Guggino SE;Guggino WB
  16. J Cell Biol v.94 The concept of lipid domains in membranes Karnovsky MJ;Kleinfeld AM;Hoover RL;Klausner RD
  17. Neuron v.5 Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals Keyser DO;Alger BE
  18. Br J Pharmacol v.109 Nitric oxide and arachidonic acid modulation of calcium currents in post-ganglionic neurones of avian cultured ciliary ganglia Khurana G;Bennett MR
  19. Science v.244 Potassium channels in cardiac cells activatef by arachidonic acid and phospholipids Kim D;Clapham DE
  20. Circ Res v.67 Regulation of $K^{+}$channels in cardiac myocytes by free fatty acids Kim D;Duff RA
  21. Mol Pharmacol v.38 Nordihydroguaiaretic acid inhibits voltage-activated $Ca{2+}$currents independently of lipoxygenase inhibition Korn SJ;Horn R
  22. J Biol Chem v.255 Lipid domains in membranes Klausner RD;Kleinfeld AM;Hoover RL;Karnovsky MJ
  23. Annu Rev Biochem v.55 Arachidonic acid metabolism Needleman P;Turk J;Jakschik BA;Morrison AR;Lefkowith JB
  24. Science v.244 Arachidonic acid and other fatty acid directly activate potassium channels in smooth muscle cells Ordway RW;Walsh JV;Singer JJ
  25. Trends Neurosci v.14 Direct regulation of ion channels by fatty acids Ordway RW;Walsh JV;Singer JJ
  26. J Neurochem v.66 Cyclic AMP-independent inhibition of voltage-sensitive calcium channels by forskolin in PC12 cells Park TJ;Kim KT
  27. Rewnds Pharmacol Sci v.14 Do the $K^{+}$channels openers relax smooth muscle by opening $K^{+}$channels? Quast U
  28. J Immunol v.138 Arachidonic acid acts as intracellular activator of NADPH-oxidase in Fc receptor-mediated superoxide generation in macrophages Sakata A;Ida E;Tominaga M;Onoeu K
  29. J Gen Physiol v.100 Modulation of voltagedependent $Ca^{2+}$channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle Shimada T;Somlyo AP
  30. Biochem Pharmacol v.47 Inhibition by ethaverine of catecholamine secretion through blocking of L-type $Ca^{2+}$channel in PC12 cells Sub BC;Kim KT
  31. J Neurosci v.7 Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons Trussell LO;Jackson MB
  32. Am J Physiol v.262 Arachidonic acid inhibits the secretory $K^{+}$channels of cortical collecting duct of rat kidney Wang W;Cassola A;Giebisch G