Modulation of muscarinic cholinoceptor-stimulated inositol 1,4,5-trisphosphate accumulation by N-methyl-d-aspartate in neonatal rat cerebral cortex

Challis, R. A. John; Mistry, Rajendra; Gray, David W.; Nahorski, Stefan R.

doi:10.1016/0028-3908(94)90092-2

Cited by 23 publications

(20 citation statements)

References 35 publications

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“…In agreement with our previous work (Challiss et al, 1994b) (Challiss et al, 1994a) (Seif el Nasr et al, 1990;Erdo & Schaefer, 1991;Chen et al, 1992;Keilhoff & Wolf, 1992;Weller et al, 1993).…”

Section: Discussionsupporting

confidence: 93%

Modulation of NMDA effects on agonist‐stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex

Mistry

Wilke

Challiss

1995

British J Pharmacology

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Section: Discussionsupporting

confidence: 93%

Modulation of NMDA effects on agonist‐stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex

Mistry

Wilke

Challiss

1995

British J Pharmacology

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“…An inhibitory effect of NMDAR activation on PLC has been described previously in CA1 neurons (40). A similar effect in cerebral cortex was irreversible, possibly reflecting NMDAinduced cellular damage (41). When (Ϯ)MCPG and (ϩ)-MK-801 were added to cells in which both NMDARs and mGluRs were stimulated (with NMDA and 1S,3R-ACPD), there was an initial increase in [Ca 2ϩ ] i , lasting approximately 90 s before [Ca 2ϩ ] i returned to control levels.…”

Section: Discussionsupporting

confidence: 76%

Expression of Functional Metabotropic Glutamate Receptors in Primary Cultured Rat Osteoblasts

Gu¹,

Publicover

2000

Journal of Biological Chemistry

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Osteoblasts and osteoclasts express functional N-methyl-D-aspartate (NMDA) receptors, which participate in regulation of bone matrix. In rat femoral osteoblasts held in whole cell clamp there is a robust NMDA current but little if any response to L- It is well established that bone cells are regulated in their activity both by circulating hormones (1) and by the interacting effects of a number of locally acting intercellular signals, including prostaglandins, growth factors, cytokines, and nitric oxide (2-9). Recently, it has been reported that functional NMDA 1 -type glutamate receptors are expressed in a number of bone cell types, including rat and human osteoblasts and osteoclasts, MG-63 osteosarcoma cells, and in bone marrow megakaryocytes (10 -15). Osteoblasts, which contain high levels of glutamate (16), express regulatory proteins required for vesicular exocytosis that co-localize with glutamate (17). In vitro, osteoblasts secrete glutamate in a regulated manner. 2Initial histochemical data show that nerve endings able to secrete L-glutamate may also occur within bone (16). Antagonists of NMDA receptors modulate the activities of both osteoblasts and osteoclasts, the bone cells responsible for deposition and resorbtion of bone matrix (10, 14, 18). These findings suggest that glutamate-mediated signaling occurs in bone, in a manner analogous to glutamatergic transmission between neurons, and that it contributes to regulation of bone matrix (19).The NMDA receptor is part of a complex glutamatergic system in the central nervous system, comprising several receptor types. Glutamate receptors can be divided into iGluRs (including the NMDA type found in bone) and mGluRs. mGluRs are G-protein-linked receptors that stimulate PLC (group 1 mGluRs) or inhibit adenyl cyclase (group 2 and group 3 mGluRs) (20). There is believed to be "cross-talk" between the different glutamate receptor subtypes, primarily by mGluRs acting to regulate activity of iGluRs (20). To date, only iGluRs, primarily the NMDA-type, have been detected in bone cells (10,11).The first electrophysiological study of the action of glutamate on bone-derived cells used the human osteoblast-like MG-63 cell line. Bath-applied L-glutamate and NMDA had very similar effects on these cells, with both agonists markedly increasing membrane conductance (21). However, during our studies on NMDA-induced currents in femoral explant-derived osteoblasts of rat (15), we made the surprising observation that the responses to NMDA and L-glutamate differed markedly. Cells that showed a well developed response to bath-applied NMDA gave only a very small current upon application of L-glutamate. This finding suggests the expression in femoral osteoblasts of a second type of glutamate receptor, which negatively modulates the NMDA receptor/channel. We have therefore looked for mGluRs in rat femoral osteoblasts and examined the effects of their activation on osteoblastic NMDA receptor/channels. We report that mGluR-1b receptors are expressed in these cells, that their activatio...

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“…Ubiquitination in Rat Cerebral Cortex-Rat cerebral cortex slices (350 ϫ 350 m) were prepared and incubated as described (40). Slices were collected by centrifugation (700 ϫ g for 2 min) and homogenized in lysis buffer, lysates were centrifuged (16,000 ϫ g for 10 min), and InsP 3 Rs were immunoprecipitated with CT1, probed in immunoblots with ␣-Ub, and reprobed with CT1.…”

Section: Methodsmentioning

confidence: 99%

Inositol 1,4,5-Trisphosphate Receptor Ubiquitination Is Mediated by Mammalian Ubc7, a Component of the Endoplasmic Reticulum-associated Degradation Pathway, and Is Inhibited by Chelation of Intracellular Zn2+

Webster

Tiwari

Weissman

et al. 2003

Journal of Biological Chemistry

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In response to activation of certain cell surface receptors, inositol 1,4,5-trisphosphate receptors (InsP 3 Rs), which are located in the endoplasmic reticulum, can be rapidly ubiquitinated and then degraded by the proteasome. Ubiquitination is mediated by the concerted action of ubiquitin-conjugating enzymes (Ubcs or E2s) and ubiquitin-protein ligases (E3s). In the present study we have examined the enzymology of ubiquitination of endogenous InsP 3 Rs in muscarinic agonist-stimulated SH-SY5Y human neuroblastoma cells, focusing our attention on two mammalian E2s, MmUbc6 and MmUbc7, that have been implicated in endoplasmic reticulum-associated degradation (ERAD) and are homologous to the yeast ERAD E2s, Ubc6p and Ubc7p. Analysis of SH-SY5Y cells stably expressing these enzymes and their dominant-negative mutants revealed that MmUbc7 mediates InsP 3 R ubiquitination and down-regulation, but that MmUbc6 does not. These data indicate that InsP 3 Rs are processed by a component of the ERAD pathway and suggest that MmUbc7 may be employed selectively to ubiquitinate proteins, like InsP 3 Rs, that are subject to regulated ERAD. Additional studies showed that the Zn 2؉ chelator N,N,N,N-tetrakis(2-pyridylmethyl)ethylenediamine blocked InsP 3 R ubiquitination, suggesting that a RING finger domain-containing E3 is also involved in this process. Finally, muscarinic agonist-induced InsP 3 R ubiquitination was seen in rat brain slices, indicating that the results obtained from SH-SY5Y cells reflect a physiological process.

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Modulation of muscarinic cholinoceptor-stimulated inositol 1,4,5-trisphosphate accumulation by N-methyl-d-aspartate in neonatal rat cerebral cortex

Cited by 23 publications

References 35 publications

Modulation of NMDA effects on agonist‐stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex

Modulation of NMDA effects on agonist‐stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex

Expression of Functional Metabotropic Glutamate Receptors in Primary Cultured Rat Osteoblasts

Inositol 1,4,5-Trisphosphate Receptor Ubiquitination Is Mediated by Mammalian Ubc7, a Component of the Endoplasmic Reticulum-associated Degradation Pathway, and Is Inhibited by Chelation of Intracellular Zn2+

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