{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:06:38Z","timestamp":1789070798213,"version":"build-2803163510"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,8,17]]},"abstract":"<jats:p>\n                    Fast excitatory neurotransmission in the central nervous system is mediated through glutamate acting on ionotropic glutamate receptors. However, glutamate acting on metabotropic glutamate receptors (mGluRs) can also exert an inhibitory action. Here, we report by immunocytochemistry and physiology, to our knowledge, the first glutamate receptor to be found in terminals of photoreceptors in the mammalian retina\u2014the group III metabotropic glutamate receptor mGluR8. Glutamate is the transmitter of photoreceptors, and thus mGluR8 functions as an autoreceptor. Activation of mGluR8 by the group III mGluR agonists\n                    <jats:sc>l<\/jats:sc>\n                    -2-amino-4-phosphonobutyrate and\n                    <jats:sc>l<\/jats:sc>\n                    -serine-\n                    <jats:italic>O<\/jats:italic>\n                    -phosphate, or by glutamate itself, evokes a decrease in the intracellular calcium ion concentration ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    ) in isolated photoreceptors. This effect is blocked by the group III mGluR antagonists (RS)-\u03b1-methyl-4-phosphonophenylglycine and (RS)-\u03b1-methylserine-\n                    <jats:italic>O<\/jats:italic>\n                    -phosphate. Agonists for other classes of glutamate receptors\u2014\n                    <jats:sc>n<\/jats:sc>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartic acid, quisqualic acid, kainic acid, or (RS)-\u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid\u2014have no effect on the [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in isolated photoreceptors. The down-regulation of the [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in photoreceptors by mGluR8 provides evidence for an inhibitory feedback loop at the photoreceptor synapse in the mammalian retina. This negative feedback may be a mechanism for the fine adjustment of the light-regulated release of glutamate from photoreceptors and may serve as a safety device against excitotoxic levels of release at this tonic synapse. Such a mechanism may provide a model for feedback inhibition in other parts of the central nervous system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.17.9909","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"9909-9914","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Modulation of the intracellular calcium concentration in photoreceptor terminals by a presynaptic metabotropic glutamate receptor"],"prefix":"10.1073","volume":"96","author":[{"given":"Peter","family":"Koulen","sequence":"first","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Hirnforschung, Abteilung f\u00fcr Neuroanatomie, Deutschordenstrasse 46, D-60528 Frankfurt am Main, Germany; and CNS Research, Novartis, CH-4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Hirnforschung, Abteilung f\u00fcr Neuroanatomie, Deutschordenstrasse 46, D-60528 Frankfurt am Main, Germany; and CNS Research, Novartis, CH-4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"W\u00e4ssle","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Hirnforschung, Abteilung f\u00fcr Neuroanatomie, Deutschordenstrasse 46, D-60528 Frankfurt am Main, Germany; and CNS Research, Novartis, CH-4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann Helmut","family":"Brandst\u00e4tter","sequence":"additional","affiliation":[{"name":"Max-Planck-Institut f\u00fcr Hirnforschung, Abteilung f\u00fcr Neuroanatomie, Deutschordenstrasse 46, D-60528 Frankfurt am Main, Germany; and CNS Research, Novartis, CH-4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,8,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-12-04006.1990"},{"key":"e_1_3_3_2_2","first-page":"399","volume-title":"Progress in Retinal Research","author":"Massey S M","year":"1990","unstructured":"S M Massey Progress in Retinal Research, eds N Osborne, J Chader (Pergamon, Oxford), pp. 399\u2013425 (1990)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903480407"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90354-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-15-04749.1996"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb00739.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-23-09298.1997"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-06-02200.1997"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6989(97)00176-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.17.030194.000335"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(94)00129-G"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.37.1.205"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90151-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6255566"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/346269a0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1990.0109"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-08-02372.1991"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-04-03075.1995"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1967.sp008307"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(88)90199-3"},{"key":"e_1_3_3_21_2","volume-title":"Antibodies: A Laboratory Manual","author":"Harlow E","year":"1988","unstructured":"E Harlow, D Lane Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. 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