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

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.