{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:06:27Z","timestamp":1790960787930,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2009,6,30]],"date-time":"2009-06-30T00:00:00Z","timestamp":1246320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:p>Sarcosine is an amino acid involved in one\u2010carbon metabolism and a promising therapy for schizophrenia because it enhances NMDA receptor (NMDAR) function by inhibiting glycine uptake. The structural similarity between sarcosine and glycine led us to hypothesize that sarcosine is also an agonist like glycine. We examined this possibility using whole\u2010cell recordings from cultured embryonic mouse hippocampal neurons. We found that sarcosine is an NMDAR co\u2010agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co\u2010agonist. This finding led us to examine whether the physiological effects of NMDAR activation with these two co\u2010agonists are the same. The difference in desensitization probably accounts for rises in intracellular Ca<jats:sup>2+<\/jats:sup>, as assessed by the fluorescent indicator fura\u2010FF, being larger when NMDAR activation occurred with sarcosine than with glycine. In addition, Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>currents following NMDAR activation were larger with sarcosine than with glycine. Compared to glycine, NMDAR\u2010mediated autaptic currents decayed faster with sarcosine suggesting that NMDAR deactivation also differs with these two co\u2010agonists. Despite these differences, NMDAR\u2010dependent neuronal death as assessed by propidium iodide was similar with both co\u2010agonists. The same was true for neuronal bursting. Thus, sarcosine may enhance NMDAR function by more than one mechanism and may have different effects from other NMDAR co\u2010agonists.<\/jats:p>","DOI":"10.1113\/jphysiol.2009.168757","type":"journal-article","created":{"date-parts":[[2009,5,12]],"date-time":"2009-05-12T00:46:07Z","timestamp":1242089167000},"page":"3207-3220","source":"Crossref","is-referenced-by-count":73,"title":["The glycine transport inhibitor sarcosine is an NMDA receptor co\u2010agonist that differs from glycine"],"prefix":"10.1113","volume":"587","author":[{"given":"Hai Xia","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Hyrc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu 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