CB<sub>1</sub> receptors are confined to the nervous system; their expression within the hippocampus is localised to the presynpatic terminals of a subset of cholecystokinin containing GABA-ergic neurones, where they inhibit GABA release. Hippocampal glutamate release is also inhibited by cannabinoids but at the site of action and receptor involved is still to be identified. Studies of K<sup>+</sup>-evoked release of [<sup>3</sup>H]D-Aspartate from rat hippocampal synaptosomes suggest anadamide may not just be acting on presynpatic cannabinoid receptors, but also directly on glutamate uptake transporters. The current study aims to characterise cannabinoid-modulation of excitatory amino acid (EAA) release and uptake from hippocampal glutamatergic nerve terminals. Glutamate release from synaptosomes was quantified using spectrofluorimetry and uptake was quantified with [<sup>3</sup>H]EAA’s. Both the cannabinoids, (WIN55,212-2 and anandamide) inhibited evoked glutamate release in the absence of calcium. Interestingly, WIN55,212-2-inhibition was blocked by SR141716A (CB<sub>1</sub> antagonist), whereas the response to anandamide was not. The non-selective EAA transporter (EAAT) blocker T3MG, inhibited anandamide-attenuation of evoked release. Anandamide reduced basal glutamate levels, where again, neither SR141716A nor capsazepine altered the response to anandamide, indicating these effects are not mediated by either CB<sub>1</sub> or TRPV1 receptors. The action of anandamide was neither mimicked by arachidonic acid, nor affected by PMSF, (FAAH, fatty acid amide hydrolase) inhibitor, suggesting anandamide metabolism to arachidonic acid by FAAH is not required. Anandamide also stimulated [<sup>3</sup>H]L-glutamic acid uptake; this was attenuated by the non-selective EAAT blocker, DL-TBOA. We suggest that the effects of anandamide are mediated by interaction of the endocannabinoid with glutamate receptors.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:439920 |
| Date | January 2007 |
| Creators | Nisha, Parihar |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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