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10. Transazetidine2 4dicarboxylic acid activates neuronal metabotropic receptors

Author

Favaron, Marco, Manev, Radmila M., Candeo, Paola, Arban, Roberto, Gabellini, Nadia, Kozikowski, Alan P., and Manev, Hari

Abstract

THE expression of metabotropic glutamate receptors (mGluRs) in primary cultures of cerebellar granule neurones can be: (i) modulated by the degree of depolarization during the culture period, rendering neurones differently sensitive to agonist-stimulated inositol phosphate (IP) hydrolysis; (ii) down-regulated by specific mGluR agonists. In this culture the new rigid glutamate analogue, (/-)-trans-azetidine-2,4-dicarboxylic acid (t-ADA) and the known mGluR agonist lS,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) stimulated IP formation in line with the depolarization-modified expression of mGluR1. However, the two compounds caused different patterns of mGluR down-regulation. The effects of t-ADA and 1S,3R-ACPD were also tested on transformed human embryonic kidney 293 cells transfected with mGluR1. Only 1S,3R-ACPD, but not t-ADA, stimulated IP hydrolysis, suggesting that t-ADA acts on a subtype of metabotropic receptors different from mGluR1. Hence, t-ADA might prove useful in differentiating the function of various mGluR subtypes.

Published
1993

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