Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor.
7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (CaR) and a chimeric receptor consisting of the agonist binding amino-terminal domain (ATD) of CaR and the seven transmembrane (7TM) domain of mGlu1b (named Ca/1b). CPCCOEt inhibited responses of (S)-glutamic acid and Ca2+ at mGlu1b and Ca/1b, applied at EC50 values, with IC50 values of 10.2 microM and 13.4 microM, respectively, whereas it was weak as an antagonist of Ca2+ at CaR. These data provides strong evidence that CPCCOEt exerts its antagonistic effect on mGlu1 solely by binding to the 7TM domain.
Bräuner-Osborne
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The NeuroScience PharmaBiotec Research Centre, Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, Copenhagen, Denmark.
Jensen
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Krogsgaard-Larsen
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D002460:Cell Line; D002678:Chimera / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000235:genetics*
C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D002867:Chromones; D018691:Excitatory Amino Acid Antagonists; D020033:Protein Isoforms; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1