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. 1986 Oct;83(20):7979–7983. doi: 10.1073/pnas.83.20.7979

Substance B: an endogenous brain factor that reverses presynaptic inhibition of acetylcholine release.

L B Pearce, C G Benishin, J R Cooper
PMCID: PMC386848  PMID: 2876431

Abstract

Evidence is presented of the existence of a substance in brain (substance B) that reverses presynaptic inhibition of evoked acetylcholine (AcCho) release. Addition of guinea pig brain synaptosomal incubation medium or whole brain extracts to assays in which 1,1-dimethyl-4-phenylpiperazinium-evoked release of [3H]AcCho from guinea pig myenteric plexus synaptosomes reversed purinergic, muscarinic, and alpha 2-adrenergic agonist inhibition. However, the extracts did not increase basal or evoked release of AcCho. Results of chromatography on Bio-Gel P-2 of a concentrated whole brain extract suggest this factor has an Mr of 700. Substance B was resistant to boiling under acid or alkaline conditions as well as incubation with phospholipase C and various proteases; ashing, however, completely destroyed activity. This endogenous factor was also found to antagonize agonist-mediated inhibition of electrically evoked contractions of myenteric plexus-longitudinal muscle strips from the guinea pig ileum. The demonstration of substance B with its ability to reverse presynaptic inhibition of AcCho release reveals one mode of presynaptic modulation.

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Selected References

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

  1. Briggs C. A., Cooper J. R. A synaptosomal preparation from the guinea pig ileum myenteric plexus. J Neurochem. 1981 Mar;36(3):1097–1108. doi: 10.1111/j.1471-4159.1981.tb01705.x. [DOI] [PubMed] [Google Scholar]
  2. Briggs C. A., Cooper J. R. Cholinergic modulation of the release of [3H]acetylcholine from synaptosomes of the myenteric plexus. J Neurochem. 1982 Feb;38(2):501–508. doi: 10.1111/j.1471-4159.1982.tb08656.x. [DOI] [PubMed] [Google Scholar]
  3. Chesselet M. F. Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis. Neuroscience. 1984 Jun;12(2):347–375. doi: 10.1016/0306-4522(84)90058-7. [DOI] [PubMed] [Google Scholar]
  4. Corrieri A. G., Barberis C., Gayet J. High affinity choline uptake and acetylcholine release by guinea pig neocortex synaptosomes: inhibition by adenosine derivatives. Biochem Pharmacol. 1981 Oct 1;30(19):2732–2734. doi: 10.1016/0006-2952(81)90550-5. [DOI] [PubMed] [Google Scholar]
  5. Cotman C. W. Isolation of synaptosomal and synaptic plasma membrane fractions. Methods Enzymol. 1974;31:445–452. doi: 10.1016/0076-6879(74)31050-6. [DOI] [PubMed] [Google Scholar]
  6. DUDEL J. THE ACTION OF INHIBITORY DRUGS ON NERVE TERMINALS IN CRAYFISH MUSCLE. Pflugers Arch Gesamte Physiol Menschen Tiere. 1965 May 10;284:81–94. doi: 10.1007/BF00412369. [DOI] [PubMed] [Google Scholar]
  7. Dubocovich M. L., Langer S. Z. Negative feed-back regulation of noradrenaline release by nerve stimulation in the perfused cat's spleen: differences in potency of phenoxybenzamine in blocking the pre- and post-synaptic adrenergic receptors. J Physiol. 1974 Mar;237(3):505–519. doi: 10.1113/jphysiol.1974.sp010495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. ECCLES J. C., ECCLES R. M., MAGNI F. Central inhibitory action attributable to presynaptic depolarization produced by muscle afferent volleys. J Physiol. 1961 Nov;159:147–166. doi: 10.1113/jphysiol.1961.sp006798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. ECCLES J. C., KOSTYUK P. G., SCHMIDT R. F. Presynaptic inhibition of the central actions of flexor reflex afferents. J Physiol. 1962 May;161:258–281. doi: 10.1113/jphysiol.1962.sp006885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Langer S. Z. Presynaptic regulation of the release of catecholamines. Pharmacol Rev. 1980 Dec;32(4):337–362. [PubMed] [Google Scholar]
  11. Marchi M., Paudice P., Caviglia A., Raiteri M. Is acetylcholine release from striatal nerve endings regulated by muscarinic autoreceptors? Eur J Pharmacol. 1983 Jul 15;91(1):63–68. doi: 10.1016/0014-2999(83)90362-x. [DOI] [PubMed] [Google Scholar]
  12. Paton W. D., Zar M. A. The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol. 1968 Jan;194(1):13–33. doi: 10.1113/jphysiol.1968.sp008392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Phillis J. W., Edstrom J. P., Kostopoulos G. K., Kirkpatrick J. R. Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex. Can J Physiol Pharmacol. 1979 Nov;57(11):1289–1312. doi: 10.1139/y79-194. [DOI] [PubMed] [Google Scholar]
  14. Phillis J. W., Kostopoulos G. K., Limacher J. J. A potent depressant action of adenine derivatives on cerebral cortical neurones. Eur J Pharmacol. 1975 Jan;30(1):125–129. doi: 10.1016/0014-2999(75)90214-9. [DOI] [PubMed] [Google Scholar]
  15. Phillis J. W., Wu P. H. The role of adenosine and its nucleotides in central synaptic transmission. Prog Neurobiol. 1981;16(3-4):187–239. doi: 10.1016/0301-0082(81)90014-9. [DOI] [PubMed] [Google Scholar]
  16. Reddington M., Lee K. S., Schubert P. An A1-adenosine receptor, characterized by [3H] cyclohexyladenosine binding, mediates the depression of evoked potentials in a rat hippocampal slice preparation. Neurosci Lett. 1982 Mar 5;28(3):275–279. doi: 10.1016/0304-3940(82)90070-2. [DOI] [PubMed] [Google Scholar]
  17. Reddington M., Schubert P. Parallel investigations of the effects of adenosine on evoked potentials and cyclic AMP accumulation in hippocampus slices of the rat. Neurosci Lett. 1979 Sep;14(1):37–42. doi: 10.1016/0304-3940(79)95340-0. [DOI] [PubMed] [Google Scholar]
  18. Reese J. H., Cooper J. R. Modulation of the release of acetylcholine from ileal synaptosomes by adenosine and adenosine 5'-triphosphate. J Pharmacol Exp Ther. 1982 Dec;223(3):612–616. [PubMed] [Google Scholar]
  19. Reese J. H., Cooper J. R. Noradrenergic inhibition of the nicotinically-stimulated release of acetylcholine from guinea-pig ileal synaptosomes. Biochem Pharmacol. 1984 Apr 1;33(7):1145–1147. doi: 10.1016/0006-2952(84)90528-8. [DOI] [PubMed] [Google Scholar]
  20. Reese J. H., Cooper J. R. Stimulation of acetylcholine release from guinea-pig ileal synaptosomes by cyclic nucleotides and forskolin. Biochem Pharmacol. 1984 Oct 1;33(19):3007–3011. doi: 10.1016/0006-2952(84)90601-4. [DOI] [PubMed] [Google Scholar]
  21. Starke K. Presynaptic receptors. Annu Rev Pharmacol Toxicol. 1981;21:7–30. doi: 10.1146/annurev.pa.21.040181.000255. [DOI] [PubMed] [Google Scholar]
  22. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1–124. doi: 10.1007/BFb0050157. [DOI] [PubMed] [Google Scholar]
  23. Vizi E. S. Presynaptic modulation of neurochemical transmission. Prog Neurobiol. 1979;12(3-4):181–290. doi: 10.1016/0301-0082(79)90011-x. [DOI] [PubMed] [Google Scholar]

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