Perkinton, Michael Shields; (1997) Regulation of glutamate exocytosis from isolated nerve terminals (synaptosomes): Role of presynaptic receptors. Doctoral thesis (Ph.D), UCL (University College London).

Preview

Text Regulation_of_glutamate_exocyt.pdf Download (6MB) | Preview

Abstract

Isolated nerve terminals (synaptosomes) can be used as a model to study glutamate exocytosis in the mammalian CNS. ω-CTx GVIA reduced Ca2+ entry into cerebrocortical synaptosomes and inhibited glutamate exocytosis. Furthermore, ω-CTx MVIIC completely inhibited glutamate exocytosis and Ca2+ influx into nerve terminals. From these toxin studies, it is proposed that glutamate transmission in the cerebral cortex may be controlled by class B N-type VSCC and class A P/Q type VSCC. In contrast, dihydropyridines did not alter glutamate release evoked by KCI, supporting the hypothesis that class C/D L-type VSCC are not coupled to release of fast acting transmitters. The role that presynaptic receptors play in the modulation of glutamate release was examined. The non-NMDA receptor agonists AMPA, kainate and domoate potentiated 4AP-evoked glutamate exocytosis and pharmacological analysis indicated the presence of a high-affinity kainate receptor (autoreceptor) on a population of cerebrocortical nerve terminals that is positively linked to glutamate exocytosis. (-)Baclofen, a GABAB receptor agonist, inhibited glutamate release from synaptosomes with a pharmacology that correlates closely with previous data indicating the presence of inhibitory GABAB receptors on glutamatergic nerve terminals (heteroreceptors). A direct reduction of Ca2+ entry into synaptosomes was observed with (-)baclofen and inhibition of glutamate release was insensitive to pertussis toxin (PTX), suggesting that GABAB receptors are negatively linked to VSCC coupled to glutamate exocytosis via a PTX-insensitive G-protein. Finally, the metabotropic glutamate receptor (mGluR) agonists 1S,3R-ACPD and L-AP4 strongly inhibited glutamate exocytosis from adult rat cerebrocortical synaptosomes, indicating that glutamate transmission in the adult mammalian CNS may be subject to modulation by presynaptic inhibitory group II and/or group III mGluRs (autoreceptors).

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as JSONCSVXML

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item