Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of glutamate receptor activation on the high-affinity sodium-dependent glutamate transport expressed in chick Bergmann glia cells was examined. Pre-exposure to glutamate produced a time- and dose-dependent decrease in 3H-labeled D-aspartate uptake. This effect could not be reproduced by selective glutamate receptor agonists. Furthermore, it was insensitive to both ionotropic and metabotropic glutamate receptor antagonists. Replacement of extracellular sodium ions with choline in the preincubation media, abolished the reduction of the uptake. When the cells were pre-exposed to competitive transportable inhibitors of the transporter, such as D-aspartate, DL-threo-hydroxyaspartate (DL-THA), and aspartate-beta-hydroxamate (ABH), the glutamate effect was mimicked. From saturation experiments, it was found that the reduction on the uptake, after glutamate treatment, is related to an increase in K(m). Interestingly, the effect is blocked by staurosporine, a Ca(2+)/diacylglycerol-dependent protein kinase (PKC) inhibitor. The present findings suggest that glutamate regulates its transport in a non-receptor fashion, a phenomena that is most probably linked to changes induced by the translocation process of the substrate through the transporter.
...
PMID:Regulation of high-affinity glutamate uptake activity in Bergmann glia cells by glutamate. 1082 82

It is pointed out that Ca(2+)-dependent modification rules for NMDA-dependent (NMDA-independent) synaptic plasticity in the striatum are similar to those in the neocortex and hippocampus (cerebellum). A unitary postsynaptic mechanism of synaptic modification is proposed. It is based on the assumption that, in diverse central nervous system structures, long-term potentiation/depression (LTP/LTD) of excitatory transmission (depression/potentiation of inhibitory transmission, LTDi/LTPi) is the result of an increasing/decreasing the number of phosphorylated AMPA and NMDA (GABA(A)) receptors. According to the suggested mechanism, Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C, whose activity is positively correlated with Ca(2+) enlargement, together with cAMP-dependent protein kinase A (cGMP-dependent protein kinase G, whose activity is negatively correlated with Ca(2+) rise) mainly phosphorylate ionotropic striatal receptors, if NMDA channels are opened (closed). Therefore, the positive/negative post-tetanic Ca(2+) shift in relation to a previous Ca(2+) rise must cause NMDA-dependent LTP+LTDi/LTD+LTPi or NMDA-independent LTD+LTPi/LTP+LTDi. Dopamine D(1)/D(2) or adenosine A(2A)/A(1) receptor activation must facilitate LTP+LTDi/LTD+LTPi due to an augmenting/lowering PKA activity. Activation of muscarinic M(1)/M(4) receptors must enhance LTP+LTDi/LTD+LTPi as a consequence of an increase/decrease in the activity of protein kinase C/A. The proposed mechanism is in agreement with known experimental data.
...
PMID:The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. I. Modification rules for excitatory and inhibitory synapses in the striatum. 1108 40

Correlated spiking activity and associated Ca(2+) waves in the developing retina are important in determining the connectivity of the visual system. Here, we show that GABA, via GABA(B) receptors, regulates the temporal characteristics of Ca(2+) waves occurring before synapse formation in the embryonic chick retina. Blocking ionotropic GABA receptors did no affect these Ca(2+) transients. However, when these receptors were blocked, GABA abolished the transients, as did the GABA(B) agonist baclofen. The action of baclofen was prevented by the GABA(B) antagonist p-3-aminopropyl-p-diethoxymethyl phosphoric acid (CGP35348). CGP35348 alone increased the duration of the transients, showing that GABA(B) receptors are tonically activated by endogenous GABA. Blocking the GABA transporter GAT-1 with 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid (SKF89976A) reduced the frequency of the transients. This reduction was prevented by CGP35348 and thus resulted from activation of GABA(B) receptors by an increase in external [GABA]. The effect of GABA(B) receptor activation persisted in the presence of activators and blockers of the cAMP-PKA pathway. Immunocytochemistry showed GABA(B) receptors and GAT-1 transporters on ganglion and amacrine cells from the earliest times when Ca(2+) waves occur (embryonic day 8). Patch-clamp recordings showed that K(+) channels on ganglion cell layer neurons are not modulated by GABA(B) receptors, whereas Ca(2+) channels are; however, Ca(2+) channel blockade with omega-conotoxin-GVIA or nimodipine did not prevent Ca(2+) waves. Thus, the regulation of Ca(2+) waves by GABA(B) receptors occurs independently of N- and L-type Ca(2+) channels and does not involve K(+) channels of the ganglion cell layer. GABA(B) receptors are likely to be of key importance in regulating retinal development.
...
PMID:GABAb receptors regulate chick retinal calcium waves. 1115 76

The peptide neurotransmitter, N-acetylaspartylglutamate (NAAG), is a selective agonist at the type 3 metabotropic glutamate receptor (mGluR3) where it acts to decrease cAMP levels. Rat cortical interneurons express both NAAG and glutamic acid decarboxylase, as well as mGluR3 mRNA. In the presence of ionotropic glutamate receptor antagonists, both NAAG and the group II metabotropic glutamate receptor agonist, DCG-IV, reduced the calcium-dependent, KCl-induced [(3)H]-GABA release from rat cortical neurons by 35%. This release process was unaffected by tetrodotoxin. The group II antagonist, ethyl glutamate, reversed the effects of DCG-IV and NAAG. The mGluR3-selective antagonist, beta-N-acetylaspartylglutamate, reversed the effect of NAAG. While pretreatment of cortical neurons with forskolin alone did not significantly affect KCl-stimulated [(3)H]-GABA-release, forskolin abolished the inhibition of release produced by NAAG. The protein kinase A inhibitor, H-89, decreased [(3)H]-GABA release while NAAG produced no additional inhibition in the presence of H-89. In contrast, the protein kinase C inhibitor, Ro 31--8220, had no effect on KCl-stimulated release, nor did it affect the inhibition of release produced by NAAG. The L-type calcium channel blocker, nifedipine, also inhibited the release of [(3)H]-GABA and coapplication with NAAG resulted in no significant additional inhibition of release. These data support the hypothesis that the inhibition of KCl-stimulated [(3)H]-GABA release by NAAG is mediated via presynaptic mGluR3 on GABAergic cortical neurons and that this effect is obtained by decreasing cAMP with a consequent decrease in protein kinase A activity and L-type calcium channel conductance.
...
PMID:NAAG inhibits KCl-induced [(3)H]-GABA release via mGluR3, cAMP, PKA and L-type calcium conductance. 1116 38

The model of simultaneous interrelated modification in the efficacy of synaptic inputs to different neurons of the olivary-cerebellar network is developed. The model is based on the following features of the network: simultaneous activation of the input layer (granule) cells and the output layer (deep cerebellar nuclei) cells by mossy fibers; simultaneous activation of Purkinje cells and cerebellar cells of the input and output layers by climbing fibers and their collaterals; the existence of local feedback excitatory, inhibitory, and disinhibitory circuits. The rise (decrease) of posttetanic Ca2+ concentration in reference to the level produced by previous stimulation causes the decrease (increase) in cGMP-dependent protein kinase G activity, and increase (decrease) inprotein phosphatase 1 activity. Subsequent dephosphorylation (phosphorylation) of ionotropic receptors results in simultaneous LTD (LTP) of the excitatory input together with the LTP (LTD) of the inhibitory input to the same neuron. The character of interrelated modifications of synapses at different cerebellar levels strongly depends on the olivary cell activity. In the presence (absence) of the signal from the inferior olive LTD (LTP) of the output cerebellar signal can be induced.
...
PMID:[Interrelated modification of excitatory and inhibitory synaptic connections in the olivary-cerebellar neuronal network]. 1119 89

ATP is an important signaling molecule in the nervous system and it's signaling is mediated through the metabotropic P2Y and ionotropic P2X receptors. ATP is known to stimulate Ca(2+) influx and phospholipase D (PLD) activity in the type-2 astrocyte cell line, RBA-2; in this study, we show that the release of preloaded [(3)H]GABA from RBA-2 cells is mediated through the P2X(7) receptors. ATP and the ATP analogue 3'-O-(4-benoylbenoyl)-adenosine-5'-triphosphate (BzATP) both stimulated [(3)H]GABA release in a concentration dependent manner, while the nonselective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), the P2X(7)-sensitive antagonist oxidized ATP (oATP), and high extracellular Mg(2+) all inhibited the ATP-stimulated [(3)H]GABA release. The ATP-stimulated [(3)H]GABA release was not affected neither by removing extracellular Na(+) nor by changes in the intracellular or extracellular Ca(2+) concentration. The GABA transporter inhibitors nipecotic acid and beta-alanine also had no effect. The ATP-stimulated [(3)H]GABA release was blocked, however, when media Cl(-) was replaced with gluconate and when extracellular HCO(3)(-) was removed. The Cl(-) channel/exchanger blockers 4,4'-diisothiocyanatostilbene-2',2'-disulfonic acid (DIDS) and 4-acetamido-4'- isothiocyanatostilbene-2',2'-disulfonic acids (SITS), but not diphenylamine-2-carboxylic acid (DPC) and furosemide, blocked the ATP-stimulated [(3)H]GABA release. The anionic selectivity of the process was F(-) > Cl(-) > Br(-) which is the same as that reported for volume-sensitive Cl(-) conductance. Treating cells with phorbol-12-myristate 13-acetate (PMA), forskolin, dibutyryl-cAMP, PD98059, neomycin, and D609 all inhibited the ATP-stimulated [(3)H]GABA release. We concluded that in RBA-2 cells, ATP stimulates [(3)H]GABA release through the P2X(7) receptors via a Cl(-)/HCO(3)(-)-dependent mechanism that is regulated by PKC, PKA, MEK/ERK, and PLD.
...
PMID:Activation of P2X(7) receptors induced [(3)H]GABA release from the RBA-2 type-2 astrocyte cell line through a Cl(-)/HCO(3)(-)-dependent mechanism. 1174 79

A model of plasticity is proposed for the olivocerebellar neural network in which the efficiency of the synaptic inputs to different neurons changes simultaneously and interdependently. This effect is based on the following functional characteristics of the network: simultaneous arrival of an afferent signal via mossy fibers to input granule cells and output neurons in the deep cerebellar nuclei; synchronous arrival of the signal from the inferior olive, via climbing fibers and their collaterals, at cells in the input and output layers, and to Purkinje cells, and the existence of local excitatory, inhibitory, and disinhibitory feedback circuits. Increases (decreases) in post-tetanic Ca2+ concentrations relative to the level evoked by the preceding stimulation in these cells are accompanied by decreases (increases) in the activity of cGMP-dependent protein kinase G, with increases (decreases) in the activity of protein phosphatase I. As a result, dephosphorylation (phosphorylation) of ionotropic receptors is accompanied by simultaneous depression (potentiation) of the excitatory input to a given neuron and potentiation (depression) of the inhibitory input to the same neuron. The depolarizing signal from the inferior olive affects synapse modification in different layers of the network in such a way that its presence (absence) depresses (potentiates) the signal sent from the output cells of the cerebellum to other structures.
...
PMID:Interrelated modification of excitatory and inhibitory connections in the olivocerebellar neural network. 1176 93

Neurotensin modulates dopaminergic transmission in the nigrostriatal system. DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa, is phosphorylated on Thr34 by cAMP-dependent protein kinase, resulting in its conversion into a potent inhibitor of protein phosphatase-1 (PP 1). Here, we examined the effect of neurotensin on DARPP-32 Thr34 phosphorylation using mouse neostriatal slices. Neurotensin stimulated DARPP-32 Thr34 phosphorylation by 4-7-fold with a K(0.5) of approximately 50 nM. The effect of neurotensin was antagonized by a combined neurotensin receptor type-1 (NTR1)/type-2 (NTR2) antagonist, SR142948. It was not antagonized by a NTR1 antagonist, SR48692 or by a NTR2 antagonist, levocabastine; neither was it antagonized by the two combined. Pretreatment with TTX or cobalt abolished the effect of neurotensin. The effect of neurotensin was antagonized by a dopamine D1 antagonist, SCH23390, and by ionotropic glutamate receptor antagonists, MK801 and CNQX. These results indicate that neurotensin stimulates the release of dopamine from nigrostriatal presynaptic terminals in an NMDA receptor- and AMPA receptor-dependent manner, leading to the increase in DARPP-32 Thr34 phosphorylation. Neurotensin stimulated the phosphorylation of Ser845 of the AMPA receptor GluR1 subunit in wild-type mice but not in DARPP-32 knockout mice. Thus, neurotensin, by stimulating the release of dopamine, activates the dopamine D1-receptor/cAMP/PKA/DARPP-32/PP 1 cascade.
...
PMID:Neurotensin regulates DARPP-32 thr34 phosphorylation in neostriatal neurons by activation of dopamine D1-type receptors. 1206 80

Glutamatergic inputs from corticostriatal and thalamostriatal pathways have been shown to modulate dopaminergic signaling in neostriatal neurons. DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of M (r) 32 kDa) is a signal transduction molecule that regulates the efficacy of dopamine signaling in neostriatal neurons. Dopamine signaling is mediated in part through phosphorylation of DARPP-32 at Thr34 by cAMP-dependent protein kinase, and antagonized by phosphorylation of DARPP-32 at Thr75 by cyclin-dependent protein kinase 5. We have now investigated the effects of the ionotropic glutamate NMDA and AMPA receptors on DARPP-32 phosphorylation in neostriatal slices. Activation of NMDA and AMPA receptors decreased the state of phosphorylation of DARPP-32 at Thr34 and Thr75. The decrease in Thr34 phosphorylation was mediated through Ca(2+) -dependent activation of the Ca(2+) -/calmodulin-dependent phosphatase, calcineurin. In contrast, the decrease in Thr75 phosphorylation was mediated through Ca(2+) -dependent activation of dephosphorylation by protein phosphatase-2A. The results provide support for a complex effect of glutamate on dopaminergic signaling through the regulation of dephosphorylation of different sites of DARPP-32 by different protein phosphatases.
...
PMID:Regulation of DARPP-32 dephosphorylation at PKA- and Cdk5-sites by NMDA and AMPA receptors: distinct roles of calcineurin and protein phosphatase-2A. 1206 42

Metabotropic glutamate receptors, unlike ionotropic receptors, exert their actions on ion channels via G-proteins coupled to second messenger systems. In the hippocampus stimulation of metabotropic receptors can lead to decreased potassium channel conductance, decreased accommodation of cell firing and inhibition of the slow calcium-dependent afterhyperpolarizing current (IAHP). Using the single-electrode voltage-clamp technique in hippocampal slice cultures of the rat, the role of protein kinases in mediating these metabotropic glutamate responses was investigated. In the presence of staurosporin, protein kinase C activation by phorbol esters and protein kinase A activation by 8-bromo-cyclic adenosine monophosphate were blocked. Under these conditions, the inhibition of IAHP by 1-amino-cyclopentyl-trans-dicarboxylate (ACPD), a metabotropic agonist, was unchanged, whilst the inward current elicited by ACPD was enhanced. These results demonstrate that, in the hippocampus, metabotropic glutamate responses persist during inhibition of protein kinase A and C activation. Furthermore, these responses are insensitive to pertussis toxin, confirming previous observations.
...
PMID:Reduction of Potassium Conductances Mediated by Metabotropic Glutamate Receptors in Rat CA3 Pyramidal Cells Does Not Require Protein Kinase C or Protein Kinase A. 1210 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---