Cloning and expression of a new member of the L-2-amino-4-phosphonobutyric acid-sensitive class of metabotropic glutamate receptors

Julie Saugstad, John (Mark) Kinzie, Eileen R. Mulvihill, Thomas P. Segerson, Gary Westbrook

Research output: Contribution to journalArticle

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Abstract

Despite the cloning of several metabotropic glutamate receptors (mGluR1-6), the activity and localization of the cloned mGluRs do not account for the action of L-2-amino-4-phosphonobutyric acid (L-AP4) on mitral/tufted cells in the rat olfactory bulb. Thus, we screened a rat olfactory bulb library for novel cDNA clones, using probes derived from mGluR1 and mGluR4. A full length cDNA clone encoding a metabotropic receptor (mGluR7) whose sequence was 69% identical to that of mGluR4 was isolated. Stimulation of mGluR7 with L-AP4 and glutamate (each at 1 mM) in stably transfected baby hamster kidney cells inhibited forskolin-stimulated cAMP formation, whereas ACPD (1 mM) and quisqualate (0.5 mM) were less effective. Inhibition of cAMP required high concentrations of agonist in the transfected cells, suggesting that inhibition of adenylate cyclase may not be the predominant transduction mechanism for this receptor in neurons. RNA blot analysis and in situ hybridization revealed that mGluR7 has an expression pattern in the central nervous system distinct from that of other L-AP4-sensitive mGluRs. Double-labeling with probes for mGluR1 and mGluR7 revealed that individual mitral/ tufted neurons in the olfactory bulb expressed both mRNAs. The expression pattern and L-AP4 sensitivity of mGluR7 suggest that it mediates inhibition of transmitter release at selected glutamatergic synapses. The coexpression of multiple mGluR mRNAs in single neurons indicates that the cellular effects of mGluR activation are likely to result from the integrated action of several receptor subtypes.

Original languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalMolecular Pharmacology
Volume45
Issue number3
StatePublished - Mar 1994

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Metabotropic Glutamate Receptors
Organism Cloning
Olfactory Bulb
Neurons
Clone Cells
Quisqualic Acid
Messenger RNA
Colforsin
Gene Library
Adenylyl Cyclases
Cricetinae
Synapses
In Situ Hybridization
Glutamic Acid
Central Nervous System
Complementary DNA
2-amino-4-phosphonobutyric acid
metabotropic glutamate receptor 7
RNA
Kidney

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cloning and expression of a new member of the L-2-amino-4-phosphonobutyric acid-sensitive class of metabotropic glutamate receptors. / Saugstad, Julie; Kinzie, John (Mark); Mulvihill, Eileen R.; Segerson, Thomas P.; Westbrook, Gary.

In: Molecular Pharmacology, Vol. 45, No. 3, 03.1994, p. 367-372.

Research output: Contribution to journalArticle

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