Skip to main content
NCBI home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1972 Nov 1;60(5):570–587. doi: 10.1085/jgp.60.5.570

Cyclic Adenosine Monophosphate in the Nervous System of Aplysia californica

II. Effect of serotonin and dopamine

Howard Cedar 1, James H Schwartz 1
PMCID: PMC2226087  PMID: 4345440

Abstract

Serotonin and dopamine, both likely transmitter substances in Aplysia, stimulated formation of adenosine-3',5' monophosphate (cAMP) in ganglia, connectives, and identified nerve cell bodies. This widespread distribution suggests that receptors for the response are localized throughout the nervous system, as is adenyl cyclase. Both synthesis of cAMP-3H from precursor previously labeled in incubations with adenine-3H and total content of cAMP were stimulated up to 15-fold. The acetylcholine analogue carbachol, glutamate, norepinephrine, and histamine were inactive. Full stimulation occurred within 2–4 min of applying serotonin; the extent of the effect was half maximal at 6µ serotonin. Even in the continued presence of serotonin, the increased cAMP diminished with time. When serotonin was removed, tissue remained refractory for 15–20 min; sensitivity returned after 25 min. Serotonin stimulated cAMP after removal of extracellular Na, K, or Cl and in isotonic sucrose, with all extracellular ions removed. Elevating Mg, which blocked the stimulation of cAMP caused by synaptic activity, did not affect the response to serotonin. Thus the response appeared to be independent of transmitter release and of changes in synaptic potentials and current flow. The role of cAMP in neuronal functioning remains to be determined. Conditions which markedly increased cAMP in neurons, however, did not affect the rate of RNA synthesis, nor did they alter the distribution of phosphorylated adenine or uridine nucleotides.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

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. Brown J. H., Makman M. H. Stimulation by dopamine of adenylate cyclase in retinal homogenates and of adenosine-3':5'-cyclic monophosphate formation in intact retina. Proc Natl Acad Sci U S A. 1972 Mar;69(3):539–543. doi: 10.1073/pnas.69.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carpenter D., Breese G., Schanberg S., Kopin I. Serotonin and dopamine: distribution and accumulation in Aplysia nervous and non-nervous tissues. Int J Neurosci. 1971 Jul;2(1):49–56. doi: 10.3109/00207457109146992. [DOI] [PubMed] [Google Scholar]
  4. Cedar H., Kandel E. R., Schwartz J. H. Cyclic adenosine monophosphate in the nervous system of Aplysia californica. I. Increased synthesis in response to synaptic stimulation. J Gen Physiol. 1972 Nov;60(5):558–569. doi: 10.1085/jgp.60.5.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chasin M., Rivkin I., Mamrak F., Samaniego S. G., Hess S. M. Alpha- and beta-adrenergic receptors as mediators of accumulation of cyclic adenosine 3',5'-monophosphate in specific areas of guinea pig brain. J Biol Chem. 1971 May 10;246(9):3037–3041. [PubMed] [Google Scholar]
  6. Chiarandini D. J., Gerschenfeld H. M. Ionic mechanism of cholinergic inhibition in molluscan neurons. Science. 1967 Jun 23;156(3782):1595–1596. doi: 10.1126/science.156.3782.1595. [DOI] [PubMed] [Google Scholar]
  7. Chiarandini D. J., Stefani E., Gerschenfeld H. M. Ionic mechanisms of cholinergic excitation in molluscan neurons. Science. 1967 Jun 23;156(3782):1597–1599. doi: 10.1126/science.156.3782.1597. [DOI] [PubMed] [Google Scholar]
  8. Coggeshall R. E. A light and electron microscope study of the abdominal ganglion of Aplysia californica. J Neurophysiol. 1967 Nov;30(6):1263–1287. doi: 10.1152/jn.1967.30.6.1263. [DOI] [PubMed] [Google Scholar]
  9. Cottrell G. A. Direct postsynaptic responses to stimulation of serotonin-containing neurones. Nature. 1970 Mar 14;225(5237):1060–1062. doi: 10.1038/2251060a0. [DOI] [PubMed] [Google Scholar]
  10. GERSCHENFELD H., TAUC L. Pharmacological specificities of neurones in an elementary central nervous system. Nature. 1961 Mar 18;189:924–925. doi: 10.1038/189924a0. [DOI] [PubMed] [Google Scholar]
  11. Gerschenfeld H. M., Ascher P., Tauc L. Two different excitatory transmitters acting on a single molluscan neurone. Nature. 1967 Jan 28;213(5074):358–359. doi: 10.1038/213358a0. [DOI] [PubMed] [Google Scholar]
  12. Gerschenfeld H. M. Serotonin: two different inhibitory actions on snail neurons. Science. 1971 Mar 26;171(3977):1252–1254. doi: 10.1126/science.171.3977.1252. [DOI] [PubMed] [Google Scholar]
  13. Gerschenfeld H. M., Stefani E. Evidence for an excitatory transmitter role of serotonin in molluscan central synapses. Adv Pharmacol. 1968;6(Pt A):369–392. doi: 10.1016/s1054-3589(08)61193-x. [DOI] [PubMed] [Google Scholar]
  14. Giller E., Jr, Schwartz J. H. Acetylcholinesterase in identified neurons of abdominal ganglion of Aplysia californica. J Neurophysiol. 1971 Jan;34(1):108–115. doi: 10.1152/jn.1971.34.1.108. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Gilman A. G., Nirenberg M. Effect of catecholamines on the adenosine 3':5'-cyclic monophosphate concentrations of clonal satellite cells of neurons. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2165–2168. doi: 10.1073/pnas.68.9.2165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ho R. J., Sutherland E. W. Formation and release of a hormone antagonist by rat adipocytes. J Biol Chem. 1971 Nov 25;246(22):6822–6827. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Kebabian J. W., Greengard P. Dopamine-sensitive adenyl cyclase: possible role in synaptic transmission. Science. 1971 Dec 24;174(4016):1346–1349. doi: 10.1126/science.174.4016.1346. [DOI] [PubMed] [Google Scholar]
  22. Kehoe J. Single presynaptic neurone mediates a two component postsynaptic inhibition. Nature. 1969 Mar 1;221(5183):866–868. doi: 10.1038/221866a0. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Krishna G., Forn J., Voigt K., Paul M., Gessa G. L. Dynamic aspects of neurohormonal control of cyclic 3',5'-AMP synthesis in brain. Adv Biochem Psychopharmacol. 1970;3:155–172. [PubMed] [Google Scholar]
  25. 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]
  26. MANSOUR T. E. The effect of lysergic acid diethylamide, 5-hydroxytryptamine, and related compounds on the liver fluke, Fasciola hepatica. Br J Pharmacol Chemother. 1957 Dec;12(4):406–409. doi: 10.1111/j.1476-5381.1957.tb00156.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. MANSOUR T. E. The effect of serotonin and related compounds on the carbohydrate metabolism of the liver fluke, Fasciola hepatica. J Pharmacol Exp Ther. 1959 Jul;126(3):212–216. [PubMed] [Google Scholar]
  28. Manganiello V. C., Murad F., Vaughan M. Effects of lipolytic and antilipolytic agents on cyclic 3',5'-adenosine monophosphate in fat cells. J Biol Chem. 1971 Apr 10;246(7):2195–2202. [PubMed] [Google Scholar]
  29. 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]
  30. Randerath K., Randerath E. Ion-exchange thin-layer chromatography. XIV. Separation of nucleotide sugars and nucleoside monophosphates on PEI-cellulose. Anal Biochem. 1965 Dec;13(3):575–579. doi: 10.1016/0003-2697(65)90356-8. [DOI] [PubMed] [Google Scholar]
  31. Robison G. A., Butcher R. W., Sutherland E. W. Adenyl cyclase as an adrenergic receptor. Ann N Y Acad Sci. 1967 Feb 10;139(3):703–723. doi: 10.1111/j.1749-6632.1967.tb41239.x. [DOI] [PubMed] [Google Scholar]
  32. SCHWARTZ J. H., LIPMANN F. Phosphate incorporation into alkaline phosphatase of E. coli. Proc Natl Acad Sci U S A. 1961 Dec 15;47:1996–2005. doi: 10.1073/pnas.47.12.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schultz J., Hamprecht B., Daly J. W. Accumulation of adenosine 3':5'-cyclic monophosphate in clonal glial cells: labeling of intracellular adenine nucleotides with radioactive adenine. Proc Natl Acad Sci U S A. 1972 May;69(5):1266–1270. doi: 10.1073/pnas.69.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Stone D. B., Mansour T. E. Phosphofructokinase from the liver fluke Fasciola hepatica. i. Activation by adenosine 3',5'-phosphate and by serotonin. Mol Pharmacol. 1967 Mar;3(2):161–176. [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES