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G-protein-coupled receptor kinases (GRKs) comprise a family of seven mammalian serine/threonine protein kinases that phosphorylate and regulate agonist-occupied or constitutively active G-protein-coupled receptors (GPCRs). Studies of the details and consequences of these mechanisms have focused heavily on the original beta-adrenoceptor kinase (beta-ARK)(More)
The intracellular concentration of free Ca2+ ([Ca2+]i) displays complex fluctuations in response to a variety of stimuli, and acts as a pluripotent signal for many neuronal functions. It is well established that various 'metabotropic' neurotransmitter receptors can mediate the mobilization of Ca2+ stores via actions of inositol-polyphosphate second(More)
Diverse patterns of Ca(2+)(i) release differentially regulate Ca(2+)-sensitive enzymes and gene transcription, and generally the extent of agonist activation of phospholipase C-linked G protein-coupled receptors determines the type of Ca(2+) signal. We have studied global Ca(2+) oscillations arising through activation of the metabotropic glutamate receptor(More)
Previously we have shown that G protein-coupled receptor kinase (GRK) 6 plays a major role in the regulation of the human M3 muscarinic acetylcholine receptor (M3 mAChR) in the human neuroblastoma SH-SY5Y. However, 30-fold overexpression of the catalytically inactive, dominant-negative K215RGRK6 produced only a 50% suppression of M3 mAChR phosphorylation(More)
The specific binding of [3H] and [32P]Ins(1,4,5)P3 to a particulate preparation of bovine adrenal cortex has been used as a radioreceptor assay to determine the concentration of Ins(1,4,5)P3 in agonist- and depolarization-stimulated rat cerebral cortex slices. The resting concentration of Ins(1,4,5)P3 in slices that had been preincubated in a physiological(More)
The ability of lithium to interfere with phosphoinositide metabolism in rat cerebral cortex slices has been examined by monitoring the accumulation of CMP-phosphatidate (CMP-PtdOH) and the reduction in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 levels. A small accumulation of [14C]CMP-PtdOH was seen in slices prelabelled with [14C]cytidine and stimulated with(More)
Carbachol stimulation of muscarinic receptors in rat cortical slices prelabelled with myo-[2-3H]inositol caused the rapid formation of a novel inositol polyphosphate. Evidence derived from its chromatographic behaviour, and from the structure of the products formed in partial dephosphorylation experiments, suggests that it is probably D-myo-inositol(More)
The ability of lithium to interfere with the metabolism of inositol phosphates in brain may underlie its therapeutic action in manic-depressive illness. In these experiments, lithium, at therapeutic concentrations, enhanced the accumulation of [3H]inositol monophosphate but suppressed the accumulation of the putative second messengers [3H]inositol(More)
The metabotropic glutamate (mGlu) receptors mGlu1 and mGlu5 mediate distinct inositol 1,4,5-trisphosphate (IP(3)) and Ca(2+) signaling patterns, governed in part by differential mechanisms of feedback regulation after activation. Single cell imaging has shown that mGlu1 receptors initiate sustained elevations in IP(3) and Ca(2+), which are sensitive to(More)
In this study the effects of cell background on the coupling of the type 1alpha metabotropic glutamate (mGlu1alpha) receptor to different G protein sub-populations by recombinant expression of this receptor subtype in baby hamster kidney (BHK) and Chinese hamster ovary (CHO) cells have been investigated. Receptor-G protein interactions were assessed using(More)