Detailseite
Projekt
Modulation of the exocytotic and carrier-mediated transmitter release by endogenous and exogenously added cannabinoids
Antragsteller
Professor Dr. Eberhard Schlicker
Fachliche Zuordnung
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Förderung
Förderung von 2008 bis 2012
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 42860621
Cannabinoid CB1 receptors inhibit the action potential-driven, exocytotic transmitter release in neurons. Rimonabant, an inverse CB1 agonist, facilitates transmitter release, probably due to interruption of an endogenous tone built up by endocannabinoids like anandamide and/or 2-arachidonoylglycerol. Their role shall be clarified by determination of transmitter release in hippocampal slices (i) exposed to inhibitors of the synthesis and degradation of either endocannabinoid or (ii) obtained from mice not expressing such enzymes. The facilitatory effect of rimonabant might also be due to the fact that the CB1 receptors are constitutively active. This shall be checked by comparing the effect of an inverse agonist and neutral antagonist at CB1 receptors on transmitter release in isolated tissues and in cells. Finally, there is almost no information as to whether CB1 receptors affect the non-exocytotic glutamate release caused by hypoxia. The occurrence of such receptors and a possible endogenous tone shall be studied in hippocampal slices from wild type mice and mice not expressing CB1 receptors or endocannabinoid-synthesizing or -degrading enzymes. The findings may contribute to a better understanding of the clinical effect of rimonabant and of the possible use of CB1 agonists as neuroprotective drugs.
DFG-Verfahren
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