Signal Transduction: G Proteins and Second Messengers

Lambert, David G.

doi:10.1093/bja/71.1.86

Cited by 32 publications

(11 citation statements)

References 62 publications

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“…This is also consistent with recent studies in a variety of cell types demonstrating that some, but not all, muscarinic receptor subtypes are coupled to inositol phospholipid-specific phospholipase C (PLC) (see [23]). Activation of this pathway leads to the release of 1,4,5-IP 3 into the cytosol, where it mobilizes intracellular stores of Ca 2 + until it is phosphorylated to form 1,3,4,5-IP 4 and/or is dephosphorylated to form various inactive metabolites (see [11]).…”

Section: Discussionsupporting

confidence: 92%

Influence of the Muscarinic Agonist Carbachol on Intracellular Ca2+ in Chicken Granulosa Cells: I. Dependence on Follicular Maturation1

Soboloff¹,

Wade²,

Wells³

et al. 1995

Biology of Reproduction

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The present study addressed the influence of follicular development on carbamylcholine chloride (Cch)-induced Ca2+ transients and inositol 1,4,5-trisphosphate (IP3) production in granulosa cells isolated from the first (F1), third (F3), and fifth and sixth (F5,6) largest follicles. Intracellular free calcium, [Ca2+]i, was measured in fura-2-loaded cells about 20-36 h after their isolation. The percentage of cells responding to a maximal stimulatory concentration of Cch (0.2 mM) was higher in the F1 (89%) granulosa cells than in cells from the F3 (68%) and the F5,6 (72%) follicles. Most of the Ca2+ transients that were elicited in F1 granulosa cells were characterized by large (696 +/- 119 nM), fast (260 +/- 55 nM/sec) increases in [Ca2]i followed by a slow, uneven decrease in [Ca2+]i to the resting concentration. In contrast, Cch-induced changes in [Ca2+]i in F3 and F5,6 granulosa cells were generally both smaller (154 +/- 37 nM and 165 +/- 37 nM, respectively) and slower (36 +/- 25 nM/sec and 46 +/- 16 nM/sec, respectively) than those observed in cells from the largest follicle. Removal of external Ca2+ did not alter the large, fast increases in [Ca2+]i; however, it nearly blocked the slow responses observed in F3 and F5,6 cells. IP, production was elevated in 3H-myo-inositol-loaded F1 granulosa cells after 1 min of Cch (0.2 mM) treatment, whereas inositol bisphosphate (IP2) production and inositol monophosphate (IP) production were elevated only after longer incubations.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 92%

Influence of the Muscarinic Agonist Carbachol on Intracellular Ca2+ in Chicken Granulosa Cells: I. Dependence on Follicular Maturation1

Soboloff¹,

Wade²,

Wells³

et al. 1995

Biology of Reproduction

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“…Possible sites of the action of anesthetics in the GPCR-mediated signal transduction pathway are divided into four target groups: 1) agonistreceptor binding, 2) G protein function, 3) effector activity (adenylate cyclase), and 4) other intracellular sites (e.g., Ca 2ϩ stores and cellular kinases) (Lambert, 1993). There are no previous reports demonstrating an effect of volatile anesthetics on CGRP receptor-mediated signal transduction, although several studies reported that volatile anesthetics affect the signal transduction pathway mediated by other GPCRs.…”

Section: The Effects Of Volatile Anesthetics On Cgrp Receptor-mediatementioning

confidence: 99%

Volatile Anesthetics Inhibit Calcitonin Gene-Related Peptide Receptor-Mediated Responses in Pithed Rats and Human Neuroblastoma Cells

Kuroda

Yoshikawa²,

Nishikawa³

et al. 2004

J Pharmacol Exp Ther

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Calcitonin gene-related peptide (CGRP) has a potent vasodilatory effect that is mediated by specific receptors predominantly coupled to the activation of adenylate cyclase. The effects of volatile anesthetics on CGRP-induced vasodilation are unclear. We studied the effects of sevoflurane and isoflurane on CGRPinduced vasodilation in pithed rats and CGRP receptor-mediated responses in SK-N-MC cells, which are used as a model system to study the CGRP receptor and its downstream pathways. Male Wistar rats were pithed by inserting a stainless steel rod into the spinal cord. Mean arterial pressure (MAP) and cardiac output were maintained at approximately 100 mm Hg and 50 ml ⅐ min Ϫ1 , respectively, with continuous infusion of noradrenaline. After 30 min of inhalation of anesthetics, CGRP (0.1, 0.3, 1.0, and 3.0 g/kg) was administered intravenously. In SK-N-MC cells, CGRP-, forskolin-, or cholera toxin-induced cAMP production was measured with or without anesthetics using radioimmunoassays. CGRP receptor binding density and affinity for the agonist were determined with (2-[125 I]iodohystidyl 10 ) CGRP with or without the anesthetics. Sevoflurane (4%) and isoflurane (2%) significantly inhibited the decrease in MAP and systemic vascular resistance. Furthermore, both anesthetics significantly inhibited CGRP-but not forskolin-induced cAMP production. Sevoflurane (4%) and isoflurane (4%) significantly inhibited cholera toxin-induced cAMP production. Both anesthetics did not affect ligand binding. These data suggest that sevoflurane and isoflurane inhibit CGRP-induced vasodilation at the site between the CGRP receptor and adenylate cyclase activation. The inhibitory site of volatile anesthetics on the CGRP receptor-mediated response involves G s protein.

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“…It would also phosphorylate the NMDA-associated ion channel (101-104), relieving the magnesium block and resulting in an enhancement of NMDA receptor activity, allowing a greater influx of calcium. Increased concentrations of intracellular calcium would promote influx of calcium via voltage-gated calcium channels (101)(102)(103), and further increasing the intracellular concentration of calcium. Increased concentrations of calcium may facilitate activation of calcium/calmodulindependent protein kinases, leading to further phosphorylation and desensitization of mu-opioid receptors (81,105), as well as leading to the activation of adenylate cyclase and increased production of cAMP (103,106).…”

Section: Glutamate and Opioid Tolerance And Dependencementioning

confidence: 99%

“…Activated PKC phosphorylates opioid receptors (96-100), leading to receptor desensitization and reduced efficacy of opioid agonist analgesics. In addition, PKC phosphorylates the NMDA-associated ion channel (101)(102)(103)(104), increasing NMDA receptor activity, and leads to increased influx of calcium. The increased intracellular concentrations of calcium produce a positive feedback loop, increasing activity of protein kinases and enhancing the phosphorylation of opioid receptors and the NMDA ion channel.…”

Section: Glutamate and Neuropathic Painmentioning

confidence: 99%

Common Mechanisms Underlying Opioid Tolerance and Dependence and Neuropathic Pain: Role of Metabotropic Glutamate Receptors

Fundytus

2000

Pain Research and Management

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It has been suggested that opioid tolerance and dependence share common mechanisms with neuropathic pain. This short review deals with the role of glutamate and glutamate receptors in opioid tolerance and dependence, and neuropathic pain. Particular attention is given to the role of metabotropic glutamate receptors (mGluRs). First, the different types of glutamate receptors, which include N-methyl-D-aspartate, alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid, kainate and mGluRs, are described. Following this, evidence suggesting that these receptors are involved in opioid tolerance and dependence are summarized. At the end of this section, a model that has been previously proposed to explain mechanisms by which mGluRs may be involved in opioid tolerance and dependence are described. Next is a discussion of the evidence suggesting that glutamate receptors are similarly involved in neuropathic pain, and also in opioid sensitivity associated with neuropathic pain. Again, a hypothetical model used to explain mechanisms by which mGluRs may be involved in neuropathic pain is briefly described. The relevance of the data is discussed in terms of some of the clinical implications of the material presented in the article. Mécanismes communs sous-jacents à la tolérance et à la dépendance aux substances opioïdes, ainsi qu'aux douleurs névropathiques : rôle des récepteurs du glutamate métabotropique RÉSUMÉ : La tolérance et la dépendance aux substances opioïdes partageraient des mécanismes communs aux douleurs névropathiques. Il sera question, dans le présent survol, du rôle du glutamate et des ré-cepteurs du glutamate dans la tolérance et la dépendance aux substances opioïdes, ainsi que dans les douleurs névropathiques. Une attention particulière est accordée au rôle des récepteurs du glutamate métabotropique (mGluR). Tout d'abord, on décrit les différents types de récepteur du glutamate, notamment le N-méthyl-D-aspartate, l'alpha-amino-3-hydroxyl-5-méthyl-isoxazole-4-acide proprionique, le kaïnate et les mGluR. Suit un résumé des données selon lesquelles ces récepteurs sont mis en cause dans la tolérance et la dépendance aux substances opioïdes. À la fin de cette partie, on décrit un modèle déjà proposé pour expliquer comment les mGluR pourraient participer à ce phénomène de tolérance et de dépendance. Ensuite, il y a une discussion sur les éléments qui donnent à penser que les récepteurs du glutamate sont également mis en cause dans les douleurs névropathiques ainsi que dans la sensibilité aux substances opioïdes, associée aux douleurs névropathiques. Encore une fois, on fait une brève description du modèle hypothétique utilisé pour expliquer comment les mGluR contribueraient aux douleurs névropathiques. La pertinence des données est ici discutée en fonction de certaines des incidences cliniques du matériel présenté dans l'article.

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Signal Transduction: G Proteins and Second Messengers

Cited by 32 publications

References 62 publications

Influence of the Muscarinic Agonist Carbachol on Intracellular Ca2+ in Chicken Granulosa Cells: I. Dependence on Follicular Maturation1

Influence of the Muscarinic Agonist Carbachol on Intracellular Ca2+ in Chicken Granulosa Cells: I. Dependence on Follicular Maturation1

Volatile Anesthetics Inhibit Calcitonin Gene-Related Peptide Receptor-Mediated Responses in Pithed Rats and Human Neuroblastoma Cells

Common Mechanisms Underlying Opioid Tolerance and Dependence and Neuropathic Pain: Role of Metabotropic Glutamate Receptors

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