{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:30:57Z","timestamp":1769301057087,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,2,11]],"date-time":"2009-02-11T00:00:00Z","timestamp":1234310400000},"content-version":"vor","delay-in-days":4212,"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":[[1997,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Glutamate and other amino acids are the main excitatory neurotransmitters in many brain regions, including the hippocampus, by activating ion channel\u2010coupled glutamate receptors, as well as metabotropic receptors linked to G proteins and second messenger systems. Several conditions which promote the release of glutamate, like frequency stimulation and hypoxia, also lead to an increase in the extracellular levels of the important neuromodulator, adenosine. We studied whether the activation of different subgroups of metabotropic glutamate receptors (mGluR) could modify the known inhibitory effects of a selective adenosine A<jats:sub>1<\/jats:sub> receptor agonist on synaptic transmission in the hippocampus. The experiments were performed on hippocampal slices taken from young (12\u201314 days old) rats. Stimulation was delivered to the Schaffer collateral\/commissural fibres, and evoked field excitatory postsynaptic potentials (fe.p.s.p.) recorded extracellularly from the stratum radiatum in the CA1 area.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The concentration\u2010response curve for the inhibitory effects of the selective adenosine A<jats:sub>1<\/jats:sub> receptor agonist, N<jats:sup>6<\/jats:sup>\u2010cyclopentyladenosine (CPA; 2\u201350\u2003n<jats:sc>M<\/jats:sc>), on the fe.p.s.p. slope (EC<jats:sub>50<\/jats:sub>=12.5 (9.2\u201317.3; 95% confidence intervals)) was displaced to the right by the group I mGluR selective agonist, (<jats:bold>R,S<\/jats:bold>)\u20103,5\u2010dihydroxyphenylglycine (DPHG; 10\u2003\u03bc<jats:sc>M<\/jats:sc>) (EC<jats:sub>50<\/jats:sub>=27.2 (21.4\u201334.5)\u2003n<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=4). The attenuation of the inhibitory effect of CPA (10\u2003n<jats:sc>M<\/jats:sc>) on the fe.p.s.p. slope by DHPG (10\u2003\u03bc<jats:sc>M<\/jats:sc>) was blocked in the presence of the mGluR antagonist (which blocks group I and II mGluR), (<jats:bold>R,S<\/jats:bold>)\u2010\u03b1\u2010methyl\u20104\u2010carboxyphenylglycine (MCPG; 500\u2003\u03bc<jats:sc>M<\/jats:sc>). DHPG (10\u2003\u03bc<jats:sc>M<\/jats:sc>) itself had an inhibitory effect of 20.1\u00b11.9% (<jats:italic>n<\/jats:italic>=4) on the fe.p.s.p. slope.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The concentration\u2010response curves for the inhibitory effects of CPA (2\u201320\u2003n<jats:sc>M<\/jats:sc>) on the fe.p.s.p. slope were not modified either in the presence of the group II mGluR selective agonist, (2<jats:bold>S<\/jats:bold>,3<jats:bold>S<\/jats:bold>,4<jats:bold>S<\/jats:bold>)\u2010\u03b1\u2010(carboxycyclopropyl)glycine (L\u2010CCG\u2010I; 1\u2003\u03bc<jats:sc>M<\/jats:sc>), or in the presence of the non\u2010selective mGluR agonist (which activates both group I and II mGluR), (1<jats:bold>S<\/jats:bold>,3<jats:bold>R<\/jats:bold>)\u20101\u2010aminocyclopentyl\u20101,3\u2010dicarboxylate (ACPD; 100\u2003\u03bc<jats:sc>M<\/jats:sc>). L\u2010CCG\u2010I had no consistent effects and ACPD (100\u2003\u03bc<jats:sc>M<\/jats:sc>) decreased by 19.4\u00b11.8% (<jats:italic>n<\/jats:italic>=4) the fe.p.s.p. slope.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The concentration\u2010response curve for the inhibitory effects of CPA (2\u2013100\u2003n<jats:sc>M<\/jats:sc>) on the fe.p.s.p. slope (EC<jats:sub>50<\/jats:sub>=8.2 (6.9\u20139.6)\u2003n<jats:sc>M<\/jats:sc>) was displaced to the right by the group III mGluR selective agonist, <jats:sc>L<\/jats:sc>\u20102\u2010amino\u20104\u2010phosphonobutyrate (<jats:sc>L<\/jats:sc>\u2010AP4; 25\u2003\u03bc<jats:sc>M<\/jats:sc>) (EC<jats:sub>50<\/jats:sub>=17.7 (13.1\u201321.9)\u2003n<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=4). The attenuation of the inhibitory effect of CPA (10\u2003n<jats:sc>M<\/jats:sc>) on the fe.p.s.p. slope by <jats:sc>L<\/jats:sc>\u2010AP4 (25\u2003\u03bc<jats:sc>M<\/jats:sc>) was blocked in the presence of the mGluR antagonist (selective for the group III mGluR), (<jats:bold>R,S<\/jats:bold>)\u2010\u03b1\u2010methyl\u20104\u2010phosphonophenylglycine (MPPG; 200\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Both the direct effect of DHPG on synaptic transmission and the attenuation of the inhibitory effect of CPA (10\u2003n<jats:sc>M<\/jats:sc>) were prevented in the presence of the protein kinase C selective inhibitors, staurosporine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) or chelerythrine (5\u2003\u03bc<jats:sc>M<\/jats:sc>), and thus attributed to activation of protein kinase C.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The attenuation by <jats:sc>L<\/jats:sc>\u2010AP4 (25\u2003\u03bc<jats:sc>M<\/jats:sc>) of the inhibitory effect of CPA (10\u2003n<jats:sc>M<\/jats:sc>) on the fe.p.s.p. slope was also prevented by the protein kinase C selective inhibitors, staurosporine (1\u2003\u03bc<jats:sc>M<\/jats:sc>) or chelerythrine (5\u2003\u03bc<jats:sc>M<\/jats:sc>), and thus attributed to activation of protein kinase C. But this effect seemed to be distinct from the direct effect of <jats:sc>L<\/jats:sc>\u2010AP4 (25\u2003\u03bc<jats:sc>M<\/jats:sc>) on synaptic transmission, which was not modified by the protein kinase C selective inhibitors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that agonists of metabotropic glutamate receptors (Groups I and III) are able to attenuate the inhibitory effects of adenosine A<jats:sub>1<\/jats:sub> receptor activation in the hippocampus. This interaction may have pathophysiological relevance in hypoxia, in which there is marked release of both excitatory amino acids and the important endogenous neuroprotective substance, adenosine.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>121<\/jats:bold>, 1541\u20131548; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701291\">10.1038\/sj.bjp.0701291<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701291","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T17:13:48Z","timestamp":1156526028000},"page":"1541-1548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Influence of metabotropic glutamate receptor agonists on the inhibitory effects of adenosine A<sub>1<\/sub> receptor activation in the rat hippocampus"],"prefix":"10.1111","volume":"121","author":[{"given":"Alexandre","family":"De Mendon\u00e7a","sequence":"first","affiliation":[]},{"given":"J. A.","family":"Ribeiro","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,2,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018901"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1984.tb05396.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.35.2.262"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65020615.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15306.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90020-5"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb16674.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91007-F"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-10-06879.1995"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-05-03370.1994"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb12780.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)91544-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01255.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199211000-00017"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00063-C"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00009a001"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.6.10.1061"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00081-G"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb01051.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00060-J"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-08-03439.1993"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1329206"},{"key":"e_1_2_6_24_1","first-page":"346","article-title":"Adenosine and brain ischemia","volume":"4","author":"Rudolphi K. A.","year":"1992","journal-title":"Cerebrovasc. Brain Metab. Rev."},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(96)10031-X"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63020769.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12051.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12729.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019168"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90227-5"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(92)90018-Q"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00560-9"},{"key":"e_1_2_6_33_1","doi-asserted-by":"crossref","first-page":"10020","DOI":"10.1016\/S0021-9258(18)90920-8","article-title":"Competitive cAMP antagonists for cAMP\u2010receptor proteins","volume":"259","author":"Haastert P. J. M.","year":"1984","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00121-X"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00093-L"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90028-0"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701291","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701291","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0701291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T19:46:05Z","timestamp":1698435965000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0701291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1997,8]]}},"alternative-id":["10.1038\/sj.bjp.0701291"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0701291","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8]]},"assertion":[{"value":"2009-02-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}