Mechanisms of [3H] gamma-aminobutyric acid release by chromaffin cells in primary culture.
The basal and evoked [3H] gamma-aminobutyric acid (GABA) release from chromaffin cells in primary cultures was studied and compared with that of [3H]NA. [3H]GABA was found to be released, in a dose-dependent fashion, by different secretagogues known to induce noradrenaline (NA) release, that is, the cholinergic agonist nicotine, high-potassium chloride, veratridine, and calcium ionophores. In general, there was a parallelism between percentages of release of both [3H]GABA and [3H]NA, although in all circumstances the former were lower. The nicotine- and high-potassium-evoked [3H]GABA release was absolutely calcium dependent, thus indicating the existence of a exocytotic-like mechanism, whereas in the veratridine-induced release, a calcium-independent component was also detected. This latter component was sodium dependent, as it showed an absolute requirement for extracellular sodium and was enhanced by ouabain. Moreover, it was inhibited by known GABA uptake inhibitors, which indicate that this component of [3H]GABA release induced by veratridine could be due to GABA outflow through the membrane carrier. The above results, together with that obtained from studies about subcellular localization of [3H]GABA taken up by chromaffin cells, seem to support the existence of two mechanisms for [3H]GABA release by chromaffin cells: one calcium-dependent, exocytotic-like, and another calcium-independent and sodium-dependent, possibly mediated by the GABA carrier. Both processes could have a functional role on the regulation of extracellular GABA levels and so in the control of catecholamine release by chromaffin cells.
Oset-Gasque
M J
MJ
Instituto de Bioquímica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Castro
E
E
González
M P
MP
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D014179:Neurotransmitter Uptake Inhibitors; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium; D009638:Norepinephrine