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PMID: 765446 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Stimulus-secretion coupling processes in brain: analysis of noradrenaline and gamma-aminobutyric acid release.

The Journal of physiology ·Vol. 254 ·No. 2 ·1976-01-00 ·Pages 475-505

Cotman CW, Haycock JW, White WF

Abstract

1. Brain synaptosomal fractions released both endogenous and exogenously loaded noradrenaline and gamma-aminobutyric acid (GABA) in response to calcium. Elevation of magnesium concentrations in the release media decreased the calcium-dependent release. 2. The release of noradrenaline and GABA occurred within 250 msec following the application of calcium. Following the initial response to calcium, release progressively decreased with continued application of calcium. GABA release declined more rapidly than noradrenaline release, consistent with a noradrenaline distribution having greater accessibility to the release process. 3. Sodium was required for the loading of noradrenaline and GABA into pools released by calcium. On the other hand, the presence of sodoium was not required for release from previously loaded pools. 4. Microsomal fractions did not exhibit calcium-dependent release of noradrenaline or GABA. Furthermore, exogenously loaded lysine was not released from synaptosomal fractions in response to calcium. 5. Barium and strontium, but not magnesium, stimulated noradrenaline and GABA release in the absence of calcium. The ordering of alkaline earth efficacies was barium greater than strontium greater than calcium. 6. Manganese inhibited calcium-dependent release of noradrenaline and GABA to a greater extent than magnesium. 7. Release, in response to 1 mM calcium, increased linearly with the log. [K+]0, suggesting that a voltage-dependent calcium inophore limits release. The slope of release vs. log. [K+]0 was greater for noradrenaline than for GABA. 8. For a given [K+]0 less than 55 mM, increases in external calcium concentration above 1 mM increased noradrenaline release but decreased GABA release. These data suggest that calcium can decrease its own permeation and that differences in the release process may exist for different neurotransmitters. 9. In the presence of the artificial calcium ionophore, A23187, both noradrenaline and GABA release increased linearly with the log. [Ca2+]0. The slope for noradrenaline release was greater than that for GABA release. 10. Stimulus-secretion coupling in brain is suggested to be regulated at the level of a voltage dependent calcium permeation mechanism. However, basic differences in the interaction of calcium with the release process may exist between the noradrenaline and GABA systems.

MeSH Terms
Aminobutyrates/metabolism Animals Barium/pharmacology Brain/metabolism Calcimycin/pharmacology Calcium/metabolism,pharmacology In Vitro Techniques Lysine/metabolism Magnesium Male Manganese/pharmacology Mice Microsomes/metabolism Norepinephrine/metabolism Potassium/metabolism Sodium/physiology Stimulation, Chemical Strontium/pharmacology Synaptosomes/drug effects,metabolism gamma-Aminobutyric Acid/metabolism
Chemicals
Aminobutyrates Barium Calcimycin Manganese gamma-Aminobutyric Acid Sodium Magnesium Lysine Potassium Calcium Norepinephrine Strontium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cotman C W
Haycock J W
White W F
References (57)
57 references, click to expand
  1. Catecholamines in fetal and newborn rat brain.
    J Neurochem. 1973 Jul;21(1):61-7 PMID: 4146461
  2. Release of noradrenaline by splenic nerve stimulation and its dependence on calcium.
    J Physiol. 1967 Jan;188(2):219-34 PMID: 6030514
  3. Exchange of neurotransmitter amino acid at nerve endings can simulate high affinity uptake.
    Nature. 1974 Aug 30;250(5469):735-7 PMID: 4153352
  4. Proceedings: Synaptosomal exchange of gamma-aminobutyric acid (GABA) can simulate high affinity uptake.
    Br J Pharmacol. 1974 Nov;52(3):435P-436P PMID: 4156487
  5. Role of transmitter uptake mechanisms in synaptic neurotransmission.
    Br J Pharmacol. 1971 Apr;41(4):571-91 PMID: 4397129
  6. Potassium-induced release of amino acids from cerebral cortex and spinal cord slices of the rat.
    Brain Res. 1974 Aug 16;76(2):297-308 PMID: 4367506
  7. Fluorometric determination of aspartate, glutamate, and gamma-aminobutyrate in nerve tissue using enzymic methods.
    Anal Biochem. 1966 Jun;15(3):487-97 PMID: 4381042
  8. Isolation of plasma membranes from rat brain.
    Biochim Biophys Acta. 1971 Sep 14;241(3):737-51 PMID: 4334345
  9. Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction.
    J Cell Biol. 1973 May;57(2):315-44 PMID: 4348786
  10. The role of calcium in the release of neurotransmitter substances and hormones.
    Pharmacol Rev. 1970 Sep;22(3):389-428 PMID: 4322219
  11. Cyclic adenosine monophosphate and norepinephrine: effects on transmembrane properties of cerebellar Purkinje cells.
    Science. 1971 Jan 15;171(3967):192-4 PMID: 4322158
  12. Mechanism of transmitter release.
    Prog Biophys Mol Biol. 1970;21:33-124 PMID: 4316709
  13. Synaptic plasma membranes from rat brain synaptosomes: isolation and partial characterization.
    Biochim Biophys Acta. 1971 Dec 3;249(2):380-94 PMID: 4257325
  14. Presynaptic regulation of catecholamine release.
    Biochem Pharmacol. 1974 Jul 1;23(13):1793-800 PMID: 4617579
  15. The interrelationship between sodium and calcium fluxes across cell membranes.
    Rev Physiol Biochem Pharmacol. 1974;70:33-82 PMID: 4618920
  16. The inhibitory effect of manganese on transmitter release at the neuromuscular junction of the toad.
    Br J Pharmacol. 1973 Feb;47(2):339-52 PMID: 4198587
  17. Stimulus secretion coupling in vitro: a rapid perfusion apparatus for monitoring efflux of transmitter substances from tissue samples.
    Anal Biochem. 1975 Jul;67(1):268-78 PMID: 238422
  18. The stimulus-induced release of acetylcholine from synaptosome beds and its calcium dependence.
    J Neurochem. 1972 Jul;19(7):1817-9 PMID: 4537789
  19. Calcium-dependent norepinephrine release from presynaptic nerve endings in vitro.
    Proc Natl Acad Sci U S A. 1972 Aug;69(8):2237-40 PMID: 4506092
  20. Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse.
    Proc Natl Acad Sci U S A. 1975 Jan;72(1):187-90 PMID: 235124
  21. Variation in noradrenaline output with changes in stimulus frequency and train length: role of different noradrenaline pools.
    Br J Pharmacol. 1974 Jul;51(3):373-81 PMID: 4451751
  22. Ultraviolet and fluorescent spectral properties of the divalent cation ionophore A23187 and its metal ion complexes.
    Biochemistry. 1974 Sep 10;13(19):4007-14 PMID: 4416784
  23. A study of the mechanism of quantal transmitter release at a chemical synapse.
    J Physiol. 1968 Nov;199(1):11-35 PMID: 4300871
  24. A study of synaptic transmission in the absence of nerve impulses.
    J Physiol. 1967 Sep;192(2):407-36 PMID: 4383089
  25. Tetrodotoxin-resistant electric activity in presynaptic terminals.
    J Physiol. 1969 Aug;203(2):459-87 PMID: 4307710
  26. Michaelis-Menten kinetics of secretion of sympathetic neurotransmitter as a function of external calcium: effect of graded alpha adrenoceptor blockade.
    Naunyn Schmiedebergs Arch Pharmacol. 1973;278(3):323-7 PMID: 4354640
  27. Morphological aspects of exocytosin in the adrenal medulla.
    Philos Trans R Soc Lond B Biol Sci. 1971 Jun 17;261(839):291-2 PMID: 4399621
  28. Use of catechol O-methyltransferase for the enzyme radiochemical assay of dopamine.
    J Neurochem. 1973 Nov;21(5):1337-40 PMID: 4761713
  29. Studies on the mechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesicles.
    Biochemistry. 1974 Jul 30;13(16):3315-30 PMID: 4842277
  30. Effects of polyvalent cations on stimulus-coupled secretion of (14C)-gamma-aminobutyric acid from isolated brain synaptosomes.
    Mol Pharmacol. 1974 May;10(3):438-49 PMID: 4851770
  31. Release of acetylcholine from hippocampal slices by potassium depolarization: dependence on high affinity choline uptake.
    Brain Res. 1974 Apr 19;70(2):372-6 PMID: 4825681
  32. Stimulus-coupled secretion of gamma-aminobutyric acid from rat brain synaptosomes.
    Science. 1973 Aug 17;181(4100):676-8 PMID: 4724481
  33. Metabolism of beds of mammalian cortical synaptosomes: response to depolarizing influences.
    J Neurochem. 1972 Mar;19(3):585-602 PMID: 5030976
  34. Studies of the uptake of 3 H-gaba and ( 3 H)glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography.
    Brain Res. 1972 Jun 8;41(1):131-43 PMID: 5036031
  35. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells.
    Br J Pharmacol. 1968 Nov;34(3):451-74 PMID: 4882190
  36. The release of dopamine from synaptosomes from rat striatum by the ionophores X 537A and A 23187.
    Biochim Biophys Acta. 1975 Jan 14;375(1):138-52 PMID: 1111574
  37. Synaptic changes in frog brain after stimulation with potassium chloride.
    J Neurocytol. 1975 Feb;4(1):33-46 PMID: 1113140
  38. Stimulation by atropine of acetylcholine release and synthesis in cortical slices from rat brain.
    Br J Pharmacol. 1970 Nov;40(3):406-17 PMID: 5497792
  39. Intraneural distribution of exogenous norepinephrine in the central nervous system of the rat.
    J Cell Biol. 1970 Feb;44(2):385-99 PMID: 5411080
  40. Cortical inhibition and gamma-aminobutyric acid.
    Exp Brain Res. 1969;9(2):137-54 PMID: 5346460
  41. Quantitative studies of norepinephrine uptake by synaptosomes.
    Biochem Pharmacol. 1968 Jun;17(6):957-64 PMID: 5661357
  42. Influence of ionic environment on acetylcholine release from the motor nerve terminals.
    Acta Physiol Scand. 1966 May;67(1):34-42 PMID: 5963300
  43. Uptake and metabolism of exogenous gamma-aminobutyric acid by subcellular particles in a sodium-containing medium.
    Biochem Pharmacol. 1965 Dec;14(12):1755-64 PMID: 5880533
  44. MEASUREMENT OF LOW ENERGY BETA-EMITTERS IN AQUEOUS SOLUTION BY LIQUID SCINTILLATION COUNTING OF EMULSIONS.
    Anal Chem. 1965 Jun;37:854-7 PMID: 14326976
  45. THE EFFECTS OF ALKALINE EARTHS AND OTHER DIVALENT CATIONS ON ADRENAL MEDULLARY SECRETION.
    J Physiol. 1964 Dec;175:231-41 PMID: 14241165
  46. The effect of calcium and magnesium on the spontaneous release of transmitter from mammalian motor nerve endings.
    J Physiol. 1961 Dec;159:507-17 PMID: 14449608
  47. The nature of the antagonism between calcium and magnesium ions at the neuromuscular junction.
    J Physiol. 1957 Oct 30;138(3):434-44 PMID: 13481883
  48. The effect of magnesium on the activity of motor nerve endings.
    J Physiol. 1954 Jun 28;124(3):553-9 PMID: 13175198
  49. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  50. Electron microscope evidence of calcium-induced exocytosis in mast cells treated with 48-80 or the ionophores A-23187 and X-537A.
    J Cell Biol. 1974 Aug;62(2):519-26 PMID: 4214825
  51. The role of calcium in depolarization-secretion coupling at the motor nerve terminal.
    J Physiol. 1973 Jan;228(2):459-97 PMID: 4346994
  52. The specific effect of potassium on transmitter release by motor nerve terminals and its inhibition by calcium.
    J Physiol. 1973 Jan;228(2):435-58 PMID: 4346993
  53. Calcium entry in response to maintained depolarization of squid axons.
    J Physiol. 1973 Jun;231(3):527-48 PMID: 4783096
  54. Effects of manganese and other agents on the calcium uptake that follows depolarization of squid axons.
    J Physiol. 1973 Jun;231(3):511-26 PMID: 4783095
  55. Calcium dependence of spontaneous acetylcholine release at mammalian motor nerve terminals.
    J Physiol. 1965 Dec;181(3):487-97 PMID: 4956407
  56. Co-operative action a calcium ions in transmitter release at the neuromuscular junction.
    J Physiol. 1967 Nov;193(2):419-32 PMID: 6065887
  57. The effects of pargyline on overflow of transmitter and uptake of noradrenaline in the cat spleen.
    Br J Pharmacol. 1973 Apr;47(4):719-28 PMID: 4353241
Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.1976.sp011241
Published
1976-01-00
Pages
475-505
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1309203
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.1976.sp011241 PMC Full Text View journal details
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