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Subtype‐specific coupling with ADP‐ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108‐15 cells
Author(s) -
Higashida Haruhiro,
Zhang JiaSheng,
Mochida Sumiko,
Chen XiaoLiang,
Shin Yeonsook,
Noda Mami,
Hossain Kazi Z.,
Hoshi Naoto,
Hashii Minako,
Shigemoto Ryuichi,
Nakanishi Shigetada,
Fukuda Yutaka,
Yokoyama Shigeru
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01751.x
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 6 , glutamate receptor , metabotropic glutamate receptor 1 , microbiology and biotechnology , metabotropic glutamate receptor 2 , chemistry , metabotropic glutamate receptor 5 , biology , receptor , biochemistry
Cyclic ADP‐ribose ( cADP‐ribose) is a putative second messenger or modulator. However, the role of cADP‐ribose in the downstream signals of the metabotropic glutamate receptors (mGluRs) is unclear. Here, we show that glutamate stimulates ADP‐ribosyl cyclase activity in rat or mouse crude membranes of retina via group III mGluRs or in superior cervical ganglion via group I mGluRs. The retina of mGluR6‐deficient mice showed no increase in the ADP‐ribosyl cyclase level in response to glutamate. GTP enhanced the initial rate of basal and glutamate‐stimulated cyclase activity. GTP‐γ‐S also stimulated basal activity. To determine whether the coupling mode of mGluRs to ADP‐ribosyl cyclase is a feature common to individual cloned mGluRs, we expressed each mGluR subtype in NG108‐15 neuroblastoma × glioma hybrid cells. The glutamate‐induced stimulation of the cyclase occurs preferentially in NG108‐15 cells over‐expressing mGluRs1, 3, 5, and 6. Cells expressing mGluR2 or mGluRs4 and 7 exhibit inhibition or no coupling, respectively. Glutamate‐induced activation or inhibition of the cyclase activity was eliminated after pre‐treatment with cholera or pertussis toxin, respectively. Thus, the subtype‐specific coupling of mGluRs to ADP‐ribosyl cyclase via G proteins suggests that some glutamate‐evoked neuronal functions are mediated by cADP‐ribose.