Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells.

Abstract

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.

• Authors: Haruhiro Higashida, Jia-Sheng Zhang, Sumiko Mochida, Xiao-Liang Chen, Yeonsook Shin, Mami Noda, Kazi Z Hossain, Naoto Hoshi, Minako Hashii, Ryuichi Shigemoto, Shigetada Nakanishi, Yutaka Fukuda, Shigeru Yokoyama
• Journal: Journal of neurochemistry (J Neurochem) Vol. 85 Issue 5 Pg. 1148-58 (Jun 2003) ISSN: 0022-3042 [Print] England
• PMID: 12753074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Metabotropic Glutamate
• Adenosine Diphosphate Ribose
• Glutamic Acid
• Guanosine Triphosphate
• Cholera Toxin
• ADP-ribosyl Cyclase

Topics

• ADP-ribosyl Cyclase (chemistry, drug effects, metabolism)
• Adenosine Diphosphate Ribose (biosynthesis)
• Animals
• Cell Membrane (enzymology)
• Cells, Cultured
• Cholera Toxin (pharmacology)
• Enzyme Activation (drug effects)
• Glioma (chemistry, metabolism)
• Glutamic Acid (pharmacology)
• Guanosine Triphosphate (analogs & derivatives, pharmacology)
• Mice
• Mice, Knockout
• Neuroblastoma (chemistry, metabolism)
• Neurons (chemistry, cytology, metabolism)
• Rats
• Rats, Wistar
• Receptors, Metabotropic Glutamate (metabolism)
• Retina (chemistry, cytology, metabolism)
• Signal Transduction (drug effects, physiology)
• Superior Cervical Ganglion (chemistry, cytology, metabolism)