Stefan R. Nahorski

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The ability of mu-opioid agonists to activate G proteins has been demonstrated by studying the binding of the GTP analogue guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) to membranes from the human neuroblastoma SH-SY5Y cell line. The potent opioid agonist fentanyl caused an approximate doubling of basal [35S]GTP gamma S binding in a(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)
In this study we have quantitatively assessed the basal turnover of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and M3-muscarinic receptor-mediated changes in phosphoinositides in the human neuroblastoma cell line, SH-SY5Y. We demonstrate that the polyphosphoinositides represent a minor fraction of the total cellular phosphoinositide pool and that(More)
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 ability of lithium to exert profound and selective psychopharmacological effects to ameliorate manic-depressive psychosis has been the focus of considerable research effort. There is increasing evidence that lithium exerts its therapeutic action by interfering with polyphosphoinositide metabolism in brain and prevention of inositol recycling by an(More)
Receptor-mediated activation of phospholipase C to generate inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a ubiquitous signalling pathway in mammalian systems. A family of three IP3 receptor subtype monomers form functional tetramers, which act as effectors for Ins(1,4,5)P3, providing a ligand-gated channel that allows Ca2+ ions to move between cellular(More)
We have investigated the effects of G protein-coupled receptor kinase (GRK) 3 and GRK6 on the phosphorylation and regulation of the M3 muscarinic acetylcholine receptor (mACh) endogenously expressed in SH-SY5Y cells. Overexpression of GRK3 or GRK6 enhanced M3 mACh receptor phosphorylation after high-concentration methacholine (100 microM, 1 min) addition.(More)