Two components of glutamate exocytosis differentially affected by presynaptic modulation.
The total Ca(2+)-dependent release of glutamate induced by depolarization of cerebrocortical nerve terminals with KCl was analyzed into a fast and a slow component. The fast component exhibited a decay time of < 1 s and accounted for 0.95 +/- 0.10 nmol of glutamate, whereas the slow component, which exhibited a decay time of 52 +/- 7 s, accounted for the release of 2.48 +/- 0.19 nmol of glutamate. These two components were differentially affected by the Ca2+ chelator BAPTA, the divalent cation Sr2+, or the botulinum neurotoxin A. The adenosine A1 receptor agonist N6-cyclohexyladenosine strongly reduced the fast component without altering the slow component. In contrast, the inhibitory effect of arachidonic acid and the facilitatory action of the metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid were observed as a decrease and an increase, respectively, in the two components. It is concluded, first, that the fast and slow components correspond to the release of docked and mobilized vesicles, respectively, and second, that presynaptic modulation more significantly alters the fast component of release.
Herrero
I
I
Departmento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
Castro
E
E
Miras-Portugal
M T
MT
Sánchez-Prieto
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D007700:Kinetics; D009465:Neuromuscular Agents / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology; D012680:Sensitivity and Specificity; D013324:Strontium / Q000494:pharmacology; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D002614:Chelating Agents; D009465:Neuromuscular Agents; D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; D016718:Arachidonic Acid; D018698:Glutamic Acid; D004533:Egtazic Acid; D010738:Type C Phospholipases; D019274:Botulinum Toxins, Type A; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D013324:Strontium