Trans-azetidine-2, 4-dicarboxylic acid activates neuronal metabotropic receptors

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

Research output: Contribution to journalArticlepeer-review

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 1S,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.

Original languageEnglish (US)
Pages (from-to)967-970
Number of pages4
JournalNeuroreport
Volume4
Issue number7
DOIs
StatePublished - Jul 1993

ASJC Scopus subject areas

  • Neuroscience(all)

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