TY - JOUR T1 - Glutamate Transporter-Mediated Glutamate Secretion in the Mammalian Pineal Gland JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10852 LP - 10863 DO - 10.1523/JNEUROSCI.0894-08.2008 VL - 28 IS - 43 AU - Mean-Hwan Kim AU - Shunsuke Uehara AU - Akiko Muroyama AU - Bertil Hille AU - Yoshinori Moriyama AU - Duk-Su Koh Y1 - 2008/10/22 UR - http://www.jneurosci.org/content/28/43/10852.abstract N2 - Glutamate transporters are expressed throughout the CNS where their major role is to clear released glutamate from presynaptic terminals. Here, we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to l-glutamate and l- or d-aspartate and depolarized the membrane in patch-clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by HPLC. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative “glutamate-induced glutamate release.” Therefore, we suggest that glutamate transporters mediate synchronized elevation of l-glutamate and thereby efficiently downregulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland. ER -