Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 May;84(10):3467–3471. doi: 10.1073/pnas.84.10.3467

Cholinergic phosphatidylinositol modulation of inhibitory, G protein-linked neurotransmitter actions: electrophysiological studies in rat hippocampus.

P F Worley, J M Baraban, M McCarren, S H Snyder, B E Alger
PMCID: PMC304892  PMID: 3106971

Abstract

In electrophysiological studies using the rat hippocampal slice preparation, cholinergic agonists and phorbol 12,13-diacetate, a stimulator of protein kinase C, block the inhibitory actions of baclofen, a gamma-aminobutyric acid B receptor agonist, and adenosine. Relative potencies of cholinergic agonists in stimulating the phosphatidylinositol system, as measured biochemically, parallel their activity in blocking adenosine assessed electrophysiologically. Electrical stimulation of cholinergic afferents also reverses adenosine's inhibitory action. These findings indicate that stimulation of protein kinase C by the phosphatidylinositol system mediates cholinergic blockade of adenosine and baclofen. As these inhibitory agonists act by way of receptors linked to GTP-binding proteins, protein kinase C's inactivation of the GTP-binding protein involved may account for this cholinergic action.

Full text

PDF
3467

Images in this article

3469Image
on p.3469
3469Image
on p.3469
3470Image
on p.3470
3470Image
on p.3470
3470Image
on p.3470

Selected References

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

  1. Alger B. E. Characteristics of a slow hyperpolarizing synaptic potential in rat hippocampal pyramidal cells in vitro. J Neurophysiol. 1984 Nov;52(5):892–910. doi: 10.1152/jn.1984.52.5.892. [DOI] [PubMed] [Google Scholar]
  2. Alger B. E., Nicoll R. A. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J Physiol. 1982 Jul;328:105–123. doi: 10.1113/jphysiol.1982.sp014255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrade R., Malenka R. C., Nicoll R. A. A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science. 1986 Dec 5;234(4781):1261–1265. doi: 10.1126/science.2430334. [DOI] [PubMed] [Google Scholar]
  4. Ault B., Nadler J. V. Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice. J Pharmacol Exp Ther. 1982 Nov;223(2):291–297. [PubMed] [Google Scholar]
  5. Baraban J. M., Snyder S. H., Alger B. E. Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2538–2542. doi: 10.1073/pnas.82.8.2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bloomfield S. A., Miller R. F. A functional organization of ON and OFF pathways in the rabbit retina. J Neurosci. 1986 Jan;6(1):1–13. doi: 10.1523/JNEUROSCI.06-01-00001.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blumberg P. M., Jaken S., König B., Sharkey N. A., Leach K. L., Jeng A. Y., Yeh E. Mechanism of action of the phorbol ester tumor promoters: specific receptors for lipophilic ligands. Biochem Pharmacol. 1984 Mar 15;33(6):933–940. doi: 10.1016/0006-2952(84)90448-9. [DOI] [PubMed] [Google Scholar]
  8. Cole A. E., Nicoll R. A. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science. 1983 Sep 23;221(4617):1299–1301. doi: 10.1126/science.6612345. [DOI] [PubMed] [Google Scholar]
  9. Cole A. E., Nicoll R. A. Characterization of a slow cholinergic post-synaptic potential recorded in vitro from rat hippocampal pyramidal cells. J Physiol. 1984 Jul;352:173–188. doi: 10.1113/jphysiol.1984.sp015285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dascal N., Lotan I., Gillo B., Lester H. A., Lass Y. Acetylcholine and phorbol esters inhibit potassium currents evoked by adenosine and cAMP in Xenopus oocytes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):6001–6005. doi: 10.1073/pnas.82.17.6001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dunwiddie T. V., Hoffer B. J. Adenine nucleotides and synaptic transmission in the in vitro rat hippocampus. Br J Pharmacol. 1980 May;69(1):59–68. doi: 10.1111/j.1476-5381.1980.tb10883.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fisher S. K., Bartus R. T. Regional differences in the coupling of muscarinic receptors to inositol phospholipid hydrolysis in guinea pig brain. J Neurochem. 1985 Oct;45(4):1085–1095. doi: 10.1111/j.1471-4159.1985.tb05527.x. [DOI] [PubMed] [Google Scholar]
  13. Fisher S. K., Figueiredo J. C., Bartus R. T. Differential stimulation of inositol phospholipid turnover in brain by analogs of oxotremorine. J Neurochem. 1984 Oct;43(4):1171–1179. doi: 10.1111/j.1471-4159.1984.tb12858.x. [DOI] [PubMed] [Google Scholar]
  14. Fisher S. K., Klinger P. D., Agranoff B. W. Muscarinic agonist binding and phospholipid turnover in brain. J Biol Chem. 1983 Jun 25;258(12):7358–7363. [PubMed] [Google Scholar]
  15. Greene R. W., Haas H. L. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices. J Physiol. 1985 Sep;366:119–127. doi: 10.1113/jphysiol.1985.sp015788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gähwiler B. H., Brown D. A. GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1558–1562. doi: 10.1073/pnas.82.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hollingsworth E. B., Daly J. W. Accumulation of inositol phosphates and cyclic AMP in guinea-pig cerebral cortical preparations. Effects of norepinephrine, histamine, carbamylcholine and 2-chloroadenosine. Biochim Biophys Acta. 1985 Nov 20;847(2):207–216. doi: 10.1016/0167-4889(85)90022-9. [DOI] [PubMed] [Google Scholar]
  18. Hollingsworth E. B., Sears E. B., Daly J. W. An activator of protein kinase C (phorbol-12-myristate-13-acetate) augments 2-chloroadenosine-elicited accumulation of cyclic AMP in guinea pig cerebral cortical particulate preparations. FEBS Lett. 1985 May 20;184(2):339–342. doi: 10.1016/0014-5793(85)80634-7. [DOI] [PubMed] [Google Scholar]
  19. Jahnsen H. The action of 5-hydroxytryptamine on neuronal membranes and synaptic transmission in area CA1 of the hippocampus in vitro. Brain Res. 1980 Sep 15;197(1):83–94. doi: 10.1016/0006-8993(80)90436-9. [DOI] [PubMed] [Google Scholar]
  20. Jakobs K. H., Bauer S., Watanabe Y. Modulation of adenylate cyclase of human platelets by phorbol ester. Impairment of the hormone-sensitive inhibitory pathway. Eur J Biochem. 1985 Sep 2;151(2):425–430. doi: 10.1111/j.1432-1033.1985.tb09119.x. [DOI] [PubMed] [Google Scholar]
  21. Karbon E. W., Shenolikar S., Enna S. J. Phorbol esters enhance neurotransmitter-stimulated cyclic AMP production in rat brain slices. J Neurochem. 1986 Nov;47(5):1566–1575. doi: 10.1111/j.1471-4159.1986.tb00796.x. [DOI] [PubMed] [Google Scholar]
  22. Katada T., Gilman A. G., Watanabe Y., Bauer S., Jakobs K. H. Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem. 1985 Sep 2;151(2):431–437. doi: 10.1111/j.1432-1033.1985.tb09120.x. [DOI] [PubMed] [Google Scholar]
  23. Lanthorn T. H., Cotman C. W. Baclofen selectively inhibits excitatory synaptic transmission in the hippocampus. Brain Res. 1981 Nov 23;225(1):171–178. doi: 10.1016/0006-8993(81)90326-7. [DOI] [PubMed] [Google Scholar]
  24. Lippa A. S., Critchett D. J., Ehlert F., Yamamura H. I., Enna S. J., Bartus R. T. Age-related alterations in neurotransmitter receptors: an electrophysiological and biochemical analysis. Neurobiol Aging. 1981 Spring;2(1):3–8. doi: 10.1016/0197-4580(81)90052-x. [DOI] [PubMed] [Google Scholar]
  25. Lippa A. S., Critchett D. J., Joseph J. A. Desensitization of muscarinic acetylcholine receptors: possible relation to receptor heterogeneity and phosphoinositides. Brain Res. 1986 Feb 26;366(1-2):98–105. doi: 10.1016/0006-8993(86)91284-9. [DOI] [PubMed] [Google Scholar]
  26. Madison D. V., Malenka R. C., Nicoll R. A. Phorbol esters block a voltage-sensitive chloride current in hippocampal pyramidal cells. Nature. 1986 Jun 12;321(6071):695–697. doi: 10.1038/321695a0. [DOI] [PubMed] [Google Scholar]
  27. Magistretti P. J., Schorderet M. Norepinephrine and histamine potentiate the increases in cyclic adenosine 3':5'-monophosphate elicited by vasoactive intestinal polypeptide in mouse cerebral cortical slices: mediation by alpha 1-adrenergic and H1-histaminergic receptors. J Neurosci. 1985 Feb;5(2):362–368. doi: 10.1523/JNEUROSCI.05-02-00362.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Malenka R. C., Madison D. V., Andrade R., Nicoll R. A. Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons. J Neurosci. 1986 Feb;6(2):475–480. doi: 10.1523/JNEUROSCI.06-02-00475.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McCormick D. A., Prince D. A. Two types of muscarinic response to acetylcholine in mammalian cortical neurons. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6344–6348. doi: 10.1073/pnas.82.18.6344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Morrison J. H., Magistretti P. J., Benoit R., Bloom F. E. The distribution and morphological characteristics of the intracortical VIP-positive cell: an immunohistochemical analysis. Brain Res. 1984 Feb 6;292(2):269–282. doi: 10.1016/0006-8993(84)90763-7. [DOI] [PubMed] [Google Scholar]
  31. Morrison J. H., Molliver M. E., Grzanna R., Coyle J. T. The intra-cortical trajectory of the coeruleo-cortical projection in the rat: a tangentially organized cortical afferent. Neuroscience. 1981;6(2):139–158. doi: 10.1016/0306-4522(81)90051-8. [DOI] [PubMed] [Google Scholar]
  32. Newberry N. R., Nicoll R. A. Comparison of the action of baclofen with gamma-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol. 1985 Mar;360:161–185. doi: 10.1113/jphysiol.1985.sp015610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nicoll R. A., Alger B. E. A simple chamber for recording from submerged brain slices. J Neurosci Methods. 1981 Aug;4(2):153–156. doi: 10.1016/0165-0270(81)90049-2. [DOI] [PubMed] [Google Scholar]
  34. Nordstedt C., Fredholm B. B. Phorbol-12,13-dibutyrate enhances the cyclic AMP accumulation in rat hippocampal slices induced by adenosine analogues. Naunyn Schmiedebergs Arch Pharmacol. 1987 Feb;335(2):136–142. doi: 10.1007/BF00177714. [DOI] [PubMed] [Google Scholar]
  35. Olpe H. R., Baudry M., Fagni L., Lynch G. The blocking action of baclofen on excitatory transmission in the rat hippocampal slice. J Neurosci. 1982 Jun;2(6):698–703. doi: 10.1523/JNEUROSCI.02-06-00698.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schubert P., Mitzdorf U. Analysis and quantitative evaluation of the depressive effect of adenosine on evoked potentials in hippocampal slices. Brain Res. 1979 Aug 17;172(1):186–190. doi: 10.1016/0006-8993(79)90910-7. [DOI] [PubMed] [Google Scholar]
  37. Segal M. The action of serotonin in the rat hippocampal slice preparation. J Physiol. 1980 Jun;303:423–439. doi: 10.1113/jphysiol.1980.sp013297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Siggins G. R., Schubert P. Adenosine depression of hippocampal neurons in vitro: an intracellular study of dose-dependent actions on synaptic and membrane potentials. Neurosci Lett. 1981 Apr 9;23(1):55–60. doi: 10.1016/0304-3940(81)90186-5. [DOI] [PubMed] [Google Scholar]
  39. Worley P. F., Baraban J. M., Colvin J. S., Snyder S. H. Inositol trisphosphate receptor localization in brain: variable stoichiometry with protein kinase C. Nature. 1987 Jan 8;325(7000):159–161. doi: 10.1038/325159a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES