{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:55:19Z","timestamp":1790852119732,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3681,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The metabotropic glutamate receptor (mGluR) agonist <jats:italic>trans<\/jats:italic>\u2010(\u00b1)\u20101\u2010amino\u20101,3\u2010cyclopentanedicarboxylic acid (<jats:italic>trans<\/jats:italic>\u2010ACPD) (10\u2013100\u2003\u03bc<jats:sc>M<\/jats:sc>) depolarized isolated frog spinal cord motoneurones, a process sensitive to kynurenate (1.0\u2003m<jats:sc>M<\/jats:sc>) and tetrodotoxin (TTX) (0.783\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the presence of NMDA open channel blockers [Mg<jats:sup>2+<\/jats:sup>; (+)\u20105\u2010methyl\u201010,11\u2010dihydro\u20105<jats:italic>H<\/jats:italic>\u2010dibenzo[<jats:italic>a,d<\/jats:italic>]cyclohepten\u20105,10\u2010imine hydrogen maleate (MK801); 3,5\u2010dimethyl\u20101\u2010adamantanamine hydrochloride (memantine)] and TTX, <jats:italic>trans<\/jats:italic>\u2010ACPD significantly potentiated NMDA\u2010induced motoneurone depolarizations, but not \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methylisoxazole\u20104\u2010proprionate (AMPA)\u2010 or kainate\u2010induced depolarizations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NMDA potentiation was blocked by (<jats:bold>RS<\/jats:bold>)\u2010\u03b1\u2010methyl\u20104\u2010carboxyphenylglycine (MCPG) (240\u2003\u03bc<jats:sc>M<\/jats:sc>), but not by \u03b1\u2010methyl\u2010(2<jats:bold>S<\/jats:bold>,3<jats:bold>S<\/jats:bold>,4<jats:bold>S<\/jats:bold>)\u2010\u03b1\u2010(carboxycyclopropyl)\u2010glycine (MCCG) (290\u2003\u03bc<jats:sc>M<\/jats:sc>) or by \u03b1\u2010methyl\u2010(<jats:bold>S<\/jats:bold>)\u20102\u2010amino\u20104\u2010phosphonobutyrate (L\u2010MAP4) (250\u2003\u03bc<jats:sc>M<\/jats:sc>), and was mimicked by 3,5\u2010dihydroxyphenylglycine (DHPG) (30\u2003\u03bc<jats:sc>M<\/jats:sc>), but not by L(+)\u20102\u2010amino\u20104\u2010phosphonobutyrate (L\u2010AP4) (100\u2003\u03bc<jats:sc>M<\/jats:sc>). Therefore, <jats:italic>trans<\/jats:italic>\u2010ACPD's facilitatory effects appear to involve group I mGluRs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Potentiation was prevented by the G\u2010protein decoupling agent pertussis toxin (3\u20136\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup>, 36\u2003h preincubation). The protein kinase C inhibitors staurosporine (2.0\u2003\u03bc<jats:sc>M<\/jats:sc>) and <jats:italic>N<\/jats:italic>\u2010(2\u2010aminoethyl)\u20105\u2010isoquinolinesulphonamide HCl (H9) (77\u2003\u03bc<jats:sc>M<\/jats:sc>) did not significantly reduce enhanced NMDA responses. Protein kinase C activation with phorbol\u201012\u2010myristate 13\u2010acetate (5.0\u2003\u03bc<jats:sc>M<\/jats:sc>) had no effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Intracellular Ca<jats:sup>2+<\/jats:sup> depletion with thapsigargin (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) (which inhibits Ca<jats:sup>2+<\/jats:sup>\/ATPase), 1,2\u2010bis(<jats:italic>O<\/jats:italic>\u2010aminophenoxy)ethane\u2010<jats:italic>N,N,N\u2032,N\u2032<\/jats:italic>\u2010tetracetic acid acetyl methyl ester (BAPTA\u2010AM) (50\u2003\u03bc<jats:sc>M<\/jats:sc>) (which buffers elevations of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>), and bathing spinal cords in nominally Ca<jats:sup>2+<\/jats:sup>\u2010free medium all reduced <jats:italic>trans<\/jats:italic>\u2010ACPD's effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The calmodulin antagonists <jats:italic>N<\/jats:italic>\u2010(6\u2010aminohexyl)\u20105\u2010chloro\u20101\u2010naphthalenesulphonamide (W7) (100\u2003\u03bc<jats:sc>M<\/jats:sc>) and chlorpromazine (100\u2003\u03bc<jats:sc>M<\/jats:sc>) diminished the potentiation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In summary, group I mGluRs selectively facilitate NMDA\u2010depolarization of frog motoneurones <jats:italic>via<\/jats:italic> a G\u2010protein, a rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> from the presumed generation of phosphoinositides, binding of Ca<jats:sup>2+<\/jats:sup> to calmodulin, and lessening of the Mg<jats:sup>2+<\/jats:sup>\u2010produced channel block of the NMDA receptor.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 333\u2013341; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702263\">10.1038\/sj.bjp.0702263<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702263","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:54:15Z","timestamp":1106942055000},"page":"333-341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Mechanisms involved in the metabotropic glutamate receptor\u2010enhancement of NMDA\u2010mediated motoneurone responses in frog spinal cord"],"prefix":"10.1111","volume":"126","author":[{"given":"Alice M","family":"Holohean","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Hackman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Davidoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.77.1.309"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(96)00101-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00390-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90745-S"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90275-P"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/347765a0"},{"key":"e_1_2_7_8_1","first-page":"143","article-title":"Excitatory amino acid receptors in the vertebrate central nervous system","volume":"40","author":"COLLINGRIDGE G.L.","year":"1989","journal-title":"Pharmacol. 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