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. 1979 Jan 15;178(1):9–13. doi: 10.1042/bj1780009

The effects of barbiturates on the metabolism of phosphatidic acid and phosphatidylinositol in rat brain synaptosomes.

J C Miller, I Leung
PMCID: PMC1186475  PMID: 435289

Abstract

Barbiturates and diphenylhydantoin inhibit the carbamoylcholine-stimulated increase in 32P incorporation into phosphatidylinositol and phosphatidic acid, but have a relatively slight effect on the incorporation of 32P into these lipids in the absence of carbamoylcholine and no effect on 32P incorporation into phosphatidylcholine and phosphatidylethanolamine. Inhibition of the carbamoylcholine-stimulated increase was observed for pentobarbital, thiopental, phenobarbital, 5-(1,3-dimethylbutyl)-5-ethylbarbiturate, (+)- and (-)-5-ethyl-N-methyl-5-propylbarbituate and diphenylhydantoin. Similar concentrations of barbiturates and diphenylhydantoin were previously reported to inhibit the K+-stimulated Ca2+ influx, and therefore other agents that affect Ca2+ influx were tested to find whether they had any effect on 32P incorporation into these lipids. K+ (35 mM) increases 32P incorporation into phosphatidic acid, but to a smaller degree than 100 micrometer-carbamoylcholine, and its effect was inhibited by pentobarbital. Veratridine (75 micrometer) does not increase 32P incorporation into either phosphatidic acid or phosphatidylinositol, but did inhibit the carbamoylcholine-stimulated increase in 32P incorporation into phosphatidylinositol. The possible relationship between the phospholipid effect and stimulated Ca2+ influx is discussed.

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Selected References

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

  1. Blaustein M. P. Barbiturates block calcium uptake by stimulated and potassium-depolarized rat sympathetic ganglia. J Pharmacol Exp Ther. 1976 Jan;196(1):80–86. [PubMed] [Google Scholar]
  2. Blaustein M. P., Ector A. C. Barbiturate inhibition of calcium uptake by depolarized nerve terminals in vitro. Mol Pharmacol. 1975 May;11(3):369–378. [PubMed] [Google Scholar]
  3. Catterall W. A., Nirenberg M. Sodium uptake associated with activation of action potential ionophores of cultured neuroblastoma and muscle cells. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3759–3763. doi: 10.1073/pnas.70.12.3759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Geison R. L., Banschbach M. W., Sadeghian K., Hokin-Neaverson M. Acetylcholine stimulation of selective increases in stearic and arachidonic acids in phosphatidic acid in mouse pancreas. Biochem Biophys Res Commun. 1976 Jan 26;68(2):343–349. doi: 10.1016/0006-291x(76)91149-9. [DOI] [PubMed] [Google Scholar]
  5. Hawthorne J. N., Bleasdale J. E. Phosphatidic acid metabolism, calcium ions and transmitter release from electrically stimulated synaptosomes. Mol Cell Biochem. 1975 Aug 30;8(2):83–87. doi: 10.1007/BF02116236. [DOI] [PubMed] [Google Scholar]
  6. Jafferji S. S., Michell R. H. Effects of calcium-antagonistic drugs on the stimulation by carbamoylcholine and histamine of phosphatidylinositol turnover in longitudinal smooth muscle of guinea-pig ileum. Biochem J. 1976 Nov 15;160(2):163–169. doi: 10.1042/bj1600163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jafferji S. S., Michell R. H. Investigation of the relationship between cell-surface calcium-ion gating and phosphatidylinositol turnover by comparison of the effects of elevated extracellular potassium ion concentration on ileium smooth muscle and pancreas. Biochem J. 1976 Nov 15;160(2):397–399. doi: 10.1042/bj1600397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Knabe J., Franz N. Barbitursäurederivate, 19. Mitt. 5-Athyl-5-propyl-1N-methylbarbitursäure. Arch Pharm (Weinheim) 1975 Apr;308(4):313–316. doi: 10.1002/ardp.19753080412. [DOI] [PubMed] [Google Scholar]
  9. Kusano K., Miledi R., Stinnakre J. Postsynaptic entry of calcium induced by transmitter action. Proc R Soc Lond B Biol Sci. 1975 Apr 29;189(1094):49–56. doi: 10.1098/rspb.1975.0040. [DOI] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Michell R. H. Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta. 1975 Mar 25;415(1):81–47. doi: 10.1016/0304-4157(75)90017-9. [DOI] [PubMed] [Google Scholar]
  12. Michell R. H., Jafferji S. S., Jones L. M. Receptor occupancy dose--response curve suggests that phosphatidyl-inositol breakdown may be intrinsic to the mechanism of the muscarinic cholinergic receptor. FEBS Lett. 1976 Oct 15;69(1):1–5. doi: 10.1016/0014-5793(76)80640-0. [DOI] [PubMed] [Google Scholar]
  13. Miller J. C. A study of the kinetics of the muscarinic effect on phosphatidylinositol and phosphatidic acid metabolism in rat brain synaptosomes. Biochem J. 1977 Dec 15;168(3):549–555. doi: 10.1042/bj1680549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nicoll R. A. Pentobarbital: differential postsynaptic actions on sympathetic ganglion cells. Science. 1978 Jan 27;199(4327):451–452. doi: 10.1126/science.202032. [DOI] [PubMed] [Google Scholar]
  15. Putney J. W., Jr Biphasic modulation of potassium release in rat parotid gland by carbachol and phenylephrine. J Pharmacol Exp Ther. 1976 Aug;198(2):375–384. [PubMed] [Google Scholar]
  16. Sohn R. S., Ferrendelli J. A. Inhibition of Ca ++ transport into rat brain synaptosomes by diphenylhydantoin (DPH). J Pharmacol Exp Ther. 1973 May;185(2):272–275. [PubMed] [Google Scholar]
  17. Stallcup W. B., Cohn M. Electrical properties of a clonal cell line as determined by measurement of ion fluxes. Exp Cell Res. 1976 Mar 15;98(2):277–284. doi: 10.1016/0014-4827(76)90439-0. [DOI] [PubMed] [Google Scholar]

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