Accession Number:

ADA439302

Title:

The Regulation of Endogenous Glutamate and GABA Release from In Vitro Preparations of Rat Striatum

Descriptive Note:

Doctoral thesis

Corporate Author:

UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD

Personal Author(s):

Report Date:

1997-01-01

Pagination or Media Count:

104.0

Abstract:

The release of the major excitatory and inhibitory neurotransmitters, glutamate and GAB A, from rat caudate-putamen CP tissue slices, and GABA release from fetal rat primary striatal cultures, were studied to ascertain key mechanisms underlying the regulation of their release. An improved, highly sensitive method of high performance liquid chromatography and electrochemical detection LCED was developed to enable the reliable measurement of these endogenous amino acids from tissue release extracts. The assay permits detection of endogenous amino acids from one milligram of CP tissue in vitro. Release of both amino acids from CP tissue was evoked by elevated levels of potassium, while the potassium channel blocker, 4-aminopyridine 4-AP, selectively released GABA. Glu was selectively released by the excitatory amino acid EAA receptor agonist, N-methyl-D-aspartate NMDA. independently of external Ca2 concentration. Ca2dependent release of Glu and GABA by potassium- and AP evoked depolarization was shown to be solely dependent on external Ca2 influx through the P-type Ca2 channel P0.005 blockade of L- and N- types of Ca2 channels did not reduce release of either amino acid. Potassium and 4-AP also evoked Ca2 dependent release of GABA from the striatal cultures GABA was also released by Glu, through a Ca2-independent process. Activation of D1 dopamine receptors elicited a significant stimulation of GABA release from striatal cultures P0.01 1, but no dopaminergic effects were observed on release of either amino acid in CP tissue slices. Potassium 50 mM KCl stimulated release of GABA from the cultures was shown to be significantly increased by bicuculline P0.05, the GABAAreceptor antagonist.

Subject Categories:

  • Anatomy and Physiology
  • Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE