Abstract
Effects of the mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) were tested on closely related mGlu6 receptors. Modulation of native calcium currents in isolated sympathetic neurons from rat superior cervical ganglion by expressed mGlu(4) and mGlu(6) receptor was used to assay receptor activity. Glutamate concentration-response curves with and without PHCCC confirmed that the drug is an allosteric modulator of mGlu(4) receptor, without direct agonist activity. Conversely, PHCCC directly activates the mGlu(6) receptor and does not enhance activity of glutamate. Therefore, PHCCC is a direct mGlu(6) receptor agonist, but lacks allosteric modulatory properties.
MeSH terms
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Allosteric Regulation
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Animals
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Benzopyrans / pharmacology*
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Calcium / metabolism
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Excitatory Amino Acid Agonists / pharmacology*
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Glutamic Acid / metabolism
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Membrane Potentials
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Neurons / drug effects*
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Neurons / metabolism
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Rats
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Receptors, Metabotropic Glutamate / agonists*
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Receptors, Metabotropic Glutamate / drug effects*
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Receptors, Metabotropic Glutamate / metabolism
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Superior Cervical Ganglion / cytology
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Superior Cervical Ganglion / drug effects*
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Superior Cervical Ganglion / metabolism
Substances
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Benzopyrans
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Excitatory Amino Acid Agonists
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N-phenyl-7-(hydroxyimino)cyclopropa(b)chromen-1a-carboxamide
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor 6
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Glutamic Acid
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Calcium
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metabotropic glutamate receptor 4