Stimulus-secretion coupling processes in brain: analysis of noradrenaline and gamma-aminobutyric acid release. 1976

C W Cotman, and J W Haycock, and W F White

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.

UI MeSH Term Description Entries
D008239 Lysine An essential amino acid. It is often added to animal feed. Enisyl,L-Lysine,Lysine Acetate,Lysine Hydrochloride,Acetate, Lysine,L Lysine
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008297 Male Males
D008345 Manganese A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt

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