Agonist analysis of 2‐(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells

Agonist analysis of 2‐(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate... 1 2‐(Carboxycyclopropyl)glycines (CCGs) are conformationally restricted glutamate analogues and consist of eight isomers including l‐ and d‐forms. The agonist potencies and selectivities of these compounds for metabotropic glutamate receptors (mGluRs) were studied by examining their effects on the signal transduction of representative mGluR1, mGluR2 and mGluR4 subtypes in Chinese hamster ovary cells expressing the individual cloned receptors. 2 Two extended isomers of l‐CCG, l‐CCG‐I and l‐CCG‐II, effectively stimulated phosphatidylinositol hydrolysis in mGluR1‐expressing cells. The rank order of potencies of these compounds was l‐glutamate > l‐CCG‐I > l‐CCG‐II. 3 l‐CCG‐I and l‐CCG‐II were effective in inhibiting the forskolin‐stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation in mGluR2‐expressing cells. Particularly, l‐CCG‐I was a potent agonist for mGluR2 with an EC50 value of 3 × 10−7 m, which was more than an order of potency greater than that of l‐glutamate. 4 l‐CCG‐I evoked an inhibition of the forskolin‐stimulated cyclic AMP production characteristic of mGluR4 with a potency comparable to l‐glutamate. 5 In contrast to the above compounds, the other CCG isomers showed no appreciable effects on the signal transduction involved in the three mGluR subtypes. 6 This investigation demonstrates not only the importance of a particular isomeric structure of CCGs in the interaction with the mGluRs but also a clear receptor subtype specificity for the CCG‐receptor interaction, and indicates that the CCG isomers would serve as useful agonists for investigation of functions of the mGluR family. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Agonist analysis of 2‐(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells

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Publisher
Wiley
Copyright
1992 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
D.O.I.
10.1111/j.1476-5381.1992.tb12780.x
Publisher site
See Article on Publisher Site

Abstract

1 2‐(Carboxycyclopropyl)glycines (CCGs) are conformationally restricted glutamate analogues and consist of eight isomers including l‐ and d‐forms. The agonist potencies and selectivities of these compounds for metabotropic glutamate receptors (mGluRs) were studied by examining their effects on the signal transduction of representative mGluR1, mGluR2 and mGluR4 subtypes in Chinese hamster ovary cells expressing the individual cloned receptors. 2 Two extended isomers of l‐CCG, l‐CCG‐I and l‐CCG‐II, effectively stimulated phosphatidylinositol hydrolysis in mGluR1‐expressing cells. The rank order of potencies of these compounds was l‐glutamate > l‐CCG‐I > l‐CCG‐II. 3 l‐CCG‐I and l‐CCG‐II were effective in inhibiting the forskolin‐stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation in mGluR2‐expressing cells. Particularly, l‐CCG‐I was a potent agonist for mGluR2 with an EC50 value of 3 × 10−7 m, which was more than an order of potency greater than that of l‐glutamate. 4 l‐CCG‐I evoked an inhibition of the forskolin‐stimulated cyclic AMP production characteristic of mGluR4 with a potency comparable to l‐glutamate. 5 In contrast to the above compounds, the other CCG isomers showed no appreciable effects on the signal transduction involved in the three mGluR subtypes. 6 This investigation demonstrates not only the importance of a particular isomeric structure of CCGs in the interaction with the mGluRs but also a clear receptor subtype specificity for the CCG‐receptor interaction, and indicates that the CCG isomers would serve as useful agonists for investigation of functions of the mGluR family.

Journal

British Journal of PharmacologyWiley

Published: Oct 1, 1992

References

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