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. 1972 Nov 1;60(5):558–569. doi: 10.1085/jgp.60.5.558

Cyclic Adenosine Monophosphate in the Nervous System of Aplysia californica

I. Increased synthesis in response to synaptic stimulation

Howard Cedar 1, Eric R Kandel 1, James H Schwartz 1
PMCID: PMC2226089  PMID: 4345439

Abstract

In the isolated abdominal ganglion of Aplysia, previously incubated in adenine-3H, the amount of 3H-labeled adenosine-3',5' monophosphate (cAMP) doubled after electrical stimulation of nerves at a physiological rate (1/sec). No change was detected after 4 min of stimulation. An increase in cAMP was first seen after 15 min; lengthening the period of stimulation to 1 hr did not increase the extent of the effect. ATP contained 50% of the total radioactivity taken up from adenine-3H, cAMP about 0.1%. During stimulation both the total amount and the specific radioactivity of adenosine triphosphate (ATP) did not change. Thus, the increased amount of radioactivity found in cAMP after stimulation represented an increase in its rate of synthesis. During stimulation formation of cAMP-3H was not altered in nerves or in the cell body of an identified neuron (R2). In addition, no changes were detected in the total amounts of cAMP in the ganglion and in the cell body of R2. It seems likely that the increase was initiated by synaptic activity rather than by action potentials. It was blocked by elevating the concentration of Mg, which also blocks synaptic activity without impairing conduction of impulses. Moreover, impulse activity induced by ouabain and glutamate did not result in increased formation of cAMP.

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Selected References

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

  1. Berry R. W. Ribonucleic acid metabolism of a single neuron: correlation with electrical activity. Science. 1969 Nov 21;166(3908):1021–1023. doi: 10.1126/science.166.3908.1021. [DOI] [PubMed] [Google Scholar]
  2. Castellucci V., Pinsker H., Kupfermann I., Kandel E. R. Neuronal mechanisms of habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science. 1970 Mar 27;167(3926):1745–1748. doi: 10.1126/science.167.3926.1745. [DOI] [PubMed] [Google Scholar]
  3. Cedar H., Schwartz J. H. Cyclic adenosine monophosphate in the nervous system of Aplysia californica. II. Effect of serotonin and dopamine. J Gen Physiol. 1972 Nov;60(5):570–587. doi: 10.1085/jgp.60.5.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DEL CASTILLO J., KATZ B. The effect of magnesium on the activity of motor nerve endings. J Physiol. 1954 Jun 28;124(3):553–559. doi: 10.1113/jphysiol.1954.sp005128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ferrendelli J. A., Steiner A. L., McDougal D. B., Jr, Kipnis D. M. The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum. Biochem Biophys Res Commun. 1970 Nov 25;41(4):1061–1067. doi: 10.1016/0006-291x(70)90193-2. [DOI] [PubMed] [Google Scholar]
  6. Gardner D., Kandel E. R. Diphasic postsynaptic potential: a chemical synapse capable of mediating conjoint excitation and inhibition. Science. 1972 May 12;176(4035):675–678. doi: 10.1126/science.176.4035.675. [DOI] [PubMed] [Google Scholar]
  7. George W. J., Polson J. B., O'Toole A. G., Goldberg N. D. Elevation of guanosine 3',5'-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Natl Acad Sci U S A. 1970 Jun;66(2):398–403. doi: 10.1073/pnas.66.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gerschenfeld H. M. Chemical transmitters in invertebrate nervous systems. Symp Soc Exp Biol. 1966;20:299–323. [PubMed] [Google Scholar]
  9. Giacobini E., Grasso A. Variations of glycolytic intermediates, phosphate compounds and pyridine nucleotides after prolonged stimulation of an isolated crustacean neurone. Acta Physiol Scand. 1966 Jan-Feb;66(1):49–57. doi: 10.1111/j.1748-1716.1966.tb03166.x. [DOI] [PubMed] [Google Scholar]
  10. Giller E., Jr, Schwartz J. H. Choline acetyltransferase in identified neurons of abdominal ganglion of Aplysia californica. J Neurophysiol. 1971 Jan;34(1):93–107. doi: 10.1152/jn.1971.34.1.93. [DOI] [PubMed] [Google Scholar]
  11. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kakiuchi S., Rall T. W., McIlwain H. The effect of electrical stimulation upon the accumulation of adenosine 3',5'-phosphate in isolated cerebral tissue. J Neurochem. 1969 Apr;16(4):485–491. doi: 10.1111/j.1471-4159.1969.tb06847.x. [DOI] [PubMed] [Google Scholar]
  13. Kakiuchi S., Rall T. W. Studies on adenosine 3',5'-phosphate in rabbit cerebral cortex. Mol Pharmacol. 1968 Jul;4(4):379–388. [PubMed] [Google Scholar]
  14. Kakiuchi S., Rall T. W. The influence of chemical agents on the accumulation of adenosine 3',5'-Phosphate in slices of rabbit cerebellum. Mol Pharmacol. 1968 Jul;4(4):367–378. [PubMed] [Google Scholar]
  15. Kandel E. R., Frazier W. T., Waziri R., Coggeshall R. E. Direct and common connections among identified neurons in Aplysia. J Neurophysiol. 1967 Nov;30(6):1352–1376. doi: 10.1152/jn.1967.30.6.1352. [DOI] [PubMed] [Google Scholar]
  16. Kernell D., Peterson R. P. The effect of spike activity versus synaptic activation on the metabolism of ribonucleic acid in a molluscan giant neurone. J Neurochem. 1970 Jul;17(7):1087–1094. doi: 10.1111/j.1471-4159.1970.tb02262.x. [DOI] [PubMed] [Google Scholar]
  17. Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
  18. Kuo J. F., Lee T. P., Reyes P. L., Walton K. G., Donnelly T. E., Jr, Greengard P. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem. 1972 Jan 10;247(1):16–22. [PubMed] [Google Scholar]
  19. Kupfermann I., Pinsker H., Castellucci V., Kandel E. R. Central and peripheral control of gill movements in Aplysia. Science. 1971 Dec 17;174(4015):1252–1256. doi: 10.1126/science.174.4015.1252. [DOI] [PubMed] [Google Scholar]
  20. LARRABEE M. G., LEICHT W. S. METABOLISM OF PHOSPHATIDYL INOSITOL AND OTHER LIPIDS IN ACTIVE NEURONES OF SYMPATHETIC GANGLIA AND OTHER PERIPHERAL NERVOUS TISSUES. THE SITE OF THE INOSITIDE EFFECT. J Neurochem. 1965 Jan;12:1–13. doi: 10.1111/j.1471-4159.1965.tb10245.x. [DOI] [PubMed] [Google Scholar]
  21. MAITRA P. K., GHOSH A., SCHOENER B., CHANCE B. TRANSIENTS IN GLYCOLYTIC METABOLISM FOLLOWING ELECTRICAL ACTIVITY IN ELECTROPHORUS. Biochim Biophys Acta. 1964 Jul 29;88:112–119. doi: 10.1016/0926-6577(64)90159-7. [DOI] [PubMed] [Google Scholar]
  22. McAfee D. A., Schorderet M., Greengard P. Adenosine 3',5'-monophosphate in nervous tissue: increase associated with synaptic transmission. Science. 1971 Mar 19;171(3976):1156–1158. doi: 10.1126/science.171.3976.1156. [DOI] [PubMed] [Google Scholar]
  23. Peterson R. P., Kernell D. Effects of nerve stimulation on the metabolism of ribonucleic acid in a molluscan giant neurone. J Neurochem. 1970 Jul;17(7):1075–1085. doi: 10.1111/j.1471-4159.1970.tb02261.x. [DOI] [PubMed] [Google Scholar]
  24. Pinsker H., Kandel E. R. Synaptic activation of an electrogenic sodium pump. Science. 1969 Feb 28;163(3870):931–935. doi: 10.1126/science.163.3870.931. [DOI] [PubMed] [Google Scholar]
  25. Sattin A., Rall T. W. The effect of adenosine and adenine nucleotides on the cyclic adenosine 3', 5'-phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol. 1970 Jan;6(1):13–23. [PubMed] [Google Scholar]
  26. Schwartz J. H., Castellucci V. F., Kandel E. R. Functioning of identified neurons and synapses in abdominal ganglion of Aplysia in absence of protein synthesis. J Neurophysiol. 1971 Nov;34(6):939–953. doi: 10.1152/jn.1971.34.6.939. [DOI] [PubMed] [Google Scholar]
  27. Shimizu H., Creveling C. R., Daly J. W. Cyclic adenosine 3',5'-monophosphate formation in brain slices: stimulation by batrachotoxin, ouabain, veratridine, and potassium ions. Mol Pharmacol. 1970 Mar;6(2):184–188. [PubMed] [Google Scholar]
  28. Shimizu H., Creveling C. R., Daly J. Stimulated formation of adenosine 3',5'-cyclic phosphate in cerebral cortex: synergism between electrical activity and biogenic amines. Proc Natl Acad Sci U S A. 1970 Apr;65(4):1033–1040. doi: 10.1073/pnas.65.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Siggins G. R., Hoffer B. J., Bloom F. E. Cyclic adenosine monophosphate: possible mediator for norepinephrine effects on cerebellar Purkinje cells. Science. 1969 Sep 5;165(3897):1018–1020. doi: 10.1126/science.165.3897.1018. [DOI] [PubMed] [Google Scholar]
  30. Tauc L. Transmission in invertebrate and vertebrate ganglia. Physiol Rev. 1967 Jul;47(3):521–593. doi: 10.1152/physrev.1967.47.3.521. [DOI] [PubMed] [Google Scholar]
  31. Wachtel H., Kandel E. R. Conversion of synaptic excitation to inhibition at a dual chemical synapse. J Neurophysiol. 1971 Jan;34(1):56–68. doi: 10.1152/jn.1971.34.1.56. [DOI] [PubMed] [Google Scholar]

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