Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells. 1275 74

Periodic and spontaneous Ca(2+) spikes are observed in neurons during development of the central nervous system, and spontaneous changes in intracellular Ca(2+) concentration in neurons play important roles in the development of neural circuits. To clarify the roles of metabotropic glutamate receptors (mGluRs) in the regulation of spontaneous Ca(2+) spikes, we investigated the effects of selective and nonselective mGluRs ligands on primary cultures of rat cortical neurons. Cultured cortical neurons expressed all eight mGluR subtypes on reverse transcription-PCR. The mGluR2 and mGluR3 agonists LY379268, LY354740, and (2R,4R)-APDC increased the amplitude but decreased the frequency of spontaneous Ca(2+) spikes in cultured cortical neurons. The effects of these mGluR2 and mGluR3 agonists were completely inhibited by the presence of a potent mGluR2 and mGluR3 antagonist, LY341495, and by pretreatment with pertussis toxin. No significant effect was observed with either activation or inhibition of mGluR1, mGluR4, mGluR5, mGluR6, mGluR7, and mGluR8 on the spontaneous Ca(2+) spikes in cultured cortical neurons. These findings indicate that, among mGluRs, the group II mGluR subtypes mGluR2 and mGluR3 play principal roles in modulation of spontaneous Ca(2+) spikes.
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PMID:Regulation of spontaneous Ca(2+) spikes by metabotropic glutamate receptors in primary cultures of rat cortical neurons. 2020 33