Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells.
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-gamma-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 x 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.
Higashida
Haruhiro
H
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. haruhiro@med.kanazawa-u.ac.jp
Zhang
Jia-Sheng
JS
Mochida
Sumiko
S
Chen
Xiao-Liang
XL
Shin
Yeonsook
Y
Noda
Mami
M
Hossain
Kazi Z
KZ
Hoshi
Naoto
N
Hashii
Minako
M
Shigemoto
Ryuichi
R
Nakanishi
Shigetada
S
Fukuda
Yutaka
Y
Yokoyama
Shigeru
S
D036541:ADP-ribosyl Cyclase / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000096:biosynthesis; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005910:Glioma / Q000737:chemistry / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012160:Retina / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017783:Superior Cervical Ganglion / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
D018094:Receptors, Metabotropic Glutamate; D000246:Adenosine Diphosphate Ribose; D018698:Glutamic Acid; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D036541:ADP-ribosyl Cyclase