The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors.
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.
Beqollari
Donald
D
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Kammermeier
Paul J
PJ
D000494:Allosteric Regulation; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000187:drug effects* / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001578:Benzopyrans; D018690:Excitatory Amino Acid Agonists; C442478:N-phenyl-7-(hydroxyimino)cyclopropa(b)chromen-1a-carboxamide; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D018698:Glutamic Acid; D002118:Calcium; C108823:metabotropic glutamate receptor 4