Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Modulatory actions of serotonin (5-hydroxytryptamine, 5-HT) on excitatory postsynaptic currents (EPSCs) were studied with whole-cell recordings from superficial dorsal horn (SDH) neurones in neonatal rat spinal cord slices. In one-third of SDH neurones, 5-HT induced a sustained potentiation of evoked EPSCs lasting for more than 30 min after wash-out. This potentiation was often preceded by a transient suppression of EPSCs. 2. Serotonin differentially modulated the frequency of miniature EPSCs recorded in the presence of tetrodotoxin (TTX) according to the SDH neurones, producing a transient suppression, a transient facilitation or a long-lasting facilitation. 3. The 5-HT1A-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) suppressed the amplitude of evoked EPSCs and frequency of miniature EPSCs in a reversible manner. In contrast, the 5-HT2-receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT induced long-lasting potentiations of EPSC amplitude and miniature EPSC frequency. 4. Neither the mean amplitude nor the kinetics of miniature EPSCs were affected by 5-HT during the sustained facilitation of miniature EPSC frequency, suggesting that the facilitatory effect of 5-HT was presynaptically mediated. The 5-HT-induced long-lasting facilitation of miniature EPSC frequency was observed also in Ca(2+)-free, Mg2+ solution. 5. The long-lasting facilitation of evoked EPSC amplitude and miniature EPSC frequency by 5-HT was mimicked by the phorbol ester, phorbol 12,13-dibutyrate (PDBu), and blocked reversibly by the protein kinase C (PKC) inhibitor, calphostin C. Forskolin applied together with 3-isobutyl-1-methylxanthine (IBMX) had no effect on the evoked EPSCs. 6. We conclude that serotonin can induce a long-lasting facilitation of evoked EPSCs and spontaneous release of excitatory transmitter at SDH synapses of rat spinal cord. Our results suggest that intracellular PKC linked to the 5-HT2 receptor may mediate this effect by directly activating the exocytotic machinery.
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PMID:Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord. 873 96

The rat stomach fundus is enriched with the 5-hydroxytryptamine (5-HT)2B receptor, a recently cloned subtype of the 5-HT2 receptor family. Unlike other members of the 5-HT2 receptor family, the 5-HT2B receptor in the rat stomach fundus was not coupled to phosphatidylinositol (PI) hydrolysis. The purpose of this study was to characterize further the signal transduction mechanism of the 5-HT2B receptor in rat stomach fundus. Nitrendipine (1 microM) inhibited the maximal contraction to 5-HT (10 microM) by approx. 60%. 5-HT contractions were inhibited by approximately the same magnitude in the absence of extracellular calcium as in the presence of nitrendipine, indicating that calcium influx through voltage-dependent calcium channels accounted fully for the dependence of the 5-HT contraction on extracellular calcium. Depletion of both extracellular calcium and intracellular calcium stores abolished 5-HT contraction. Ryanodine (30 microM), an inhibitor of calcium release from internal stores, inhibited significantly the nitrendipine-insensitive 5-HT contraction, suggesting that this component of the contraction was due to calcium release from a ryanodine-sensitive site. Bisindolylmaleimide (5 microM), a specific inhibitor of protein kinase C (PKC), inhibited 5-HT contraction in either the absence or presence of nitrendipine, suggesting that activation of PKC is also important. Taken together, these data indicate that the 5-HT2B contractile receptor in the rat stomach fundus is coupled to calcium influx through voltage-dependent calcium channels, intracellular calcium release, and activation of PKC. These actions may reflect a novel coupling mechanism unrelated to increases in PI hydrolysis.
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PMID:5-HT2B receptor signaling in the rat stomach fundus: dependence on calcium influx, calcium release and protein kinase C. 878 21

Modulation of N-methyl-D-aspartate (NMDA) receptor-mediated ion currents by serotonin was investigated with a two-electrode voltage clamp technique in Xenopus oocytes injected with rat brain RNA. After a 1-min application of 200 nM serotonin a transient potentiation of the NMDA receptor-mediated ion currents was observed. The serotonin-induced enhancement was mimicked by the protein kinase C activators 1-oleoyl-2-acetyl-sn-glycerol (100 microM) and phorbol 12-myristate 13-acetate (10 nM), whereas the inactive phorbol ester 4-alpha-phorbol 12-myristate 13-acetate (10 nM) had no effect. From these observations it was concluded that protein kinase C was involved in the enhancement of NMDA-induced currents. In agreement with this conclusion, it was found that the serotonin effect was inhibited by the protein kinase C inhibitors sphingosine (1 microM) or staurosporine (1 microM) added 20 min before NMDA application and by oocyte injection of protein kinase C (PKC)-inhibitor peptide (500 ng/oocyte) 1 hr prior to recordings. The serotonin receptor involved was identified as a 5-HT2 receptor subtype by the finding that 200 nM of the selective 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine mimicked the potentiation of NMDA-induced ion currents by serotonin. Furthermore, the observed potentiation was significantly reduced by co-application of serotonin with 100 microM of the selective 5-HT2 receptor antagonist ketanserin. These results indicate that 5-HT2 receptors enhance NMDA receptor function via phosphoinositol hydrolysis and subsequent stimulation of PKC.
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PMID:Serotonin 5-HT2 receptor activation potentiates N-methyl-D-aspartate receptor-mediated ion currents by a protein kinase C-dependent mechanism. 884 32

1. The modulatory effect of serotonin (5-hydroxytryptamine, 5-HT), on the glycine (Gly) response was investigated in neurones acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using a nystatin-perforated patch recording configuration. 2. 5-HT potentiated the 10(-5) M Gly-induced Cl- current (IGly) in a concentration-dependent manner without changing the reversal potential of the Gly response or the affinity of Gly to its receptor. 3. alpha-Methyl-5-HT mimicked and ketanserine blocked the 5-HT action on IGly, thus indicating the 5-HT2 receptor-mediated enhancement. 4. Phorbol-12-myristate-13-acetate and 1-oleoyl-2-acetylglycerol potentiated IGly. The subsequent application of 5-HT slightly increase IGly. Chelerythrine blocked the enhancement of IGly by 5-HT, thus suggesting the involvement of protein kinase C (PKC) in the pathway of 5-HT action on IGly. 5. Pertussis toxin (IAP) treatment did not block the facilitatory effect of 5-HT on IGly. 6. BAPTA AM did not disturb the 5-HT-induced potentiation of IGly, thus suggesting that [Ca2+]i is not involved in the 5-HT effect. 7. In conclusion, activation of a 5-HT2 receptor coupled to an IAP-insensitive G-protein increases intracellular diacylglycerol (DAG) formation. The accumulation of DAG also increases the Ca(2+)-independent PKC activity, thus resulting in the potentiation of the Gly response in the SDCN neurones.
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PMID:Protein kinase C-mediated enhancement of glycine response in rat sacral dorsal commissural neurones by serotonin. 891 Feb 32

We investigated the effects of serotonin (5-hydroxytryptamine; 5-HT) on nitric oxide (NO) synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of NO, and the expression of inducible NO synthase protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1beta (10 ng/ml) caused a significant increase in nitrite production. 5-HT inhibited nitrite production by interleukin-1beta -stimulated vascular smooth muscle cells in a concentration-dependent manner (10(-8)-10(-5) M). 5-HT-induced inhibition of nitrite production was accompanied by decreased inducible NO synthase protein accumulation in vascular smooth muscle cells. Addition of the 5-HT2 receptor antagonist ketanserin, but not the 5-HT1A receptor antagonist spiroxatrine, inhibited the effect of 5-HT. On the other hand, the 5-HT2 receptor agonist alpha-methyl-5-HT, but not the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin, decreased interleukin-1beta-induced nitrite production by vascular smooth muscle cells. 5-HT significantly increased protein kinase C activity in vascular smooth muscle cells, and the protein kinase C inhibitor calphostin C dose-dependently abolished the effect of 5-HT on nitrite production. After protein kinase C activity was functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate for 24 h, the effect of 5-HT was abolished. These results indicate that 5-HT acts on 5-HT2 receptors and inhibits NO synthesis in interleukin-1beta-stimulated vascular smooth muscle cells at least partially through a protein kinase C-dependent pathway.
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PMID:Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1. 940 9

The present study elucidated the precise mechanism of 5-hydroxytryptamine (5-HT)-induced increase of intracellular Ca2+ concentration ([Ca2+]i) in cultured vascular smooth muscle cells isolated from rat aortic media. [Ca2+]i was measured using fluorescent Ca2+ indicator, fura-2. 5-HT caused a dose-dependent increase in [Ca2+]i, which was completely inhibited by ketanserin. alpha-Methyl-5-HT had an equipotent effect to 5-HT. Diltiazem at 10 microM partially suppressed the 5-HT-induced increase in [Ca2+]i. 5-HT also augmented Mn2+ influx, when monitored by Mn2+ quenching of fura-2 fluorescence. When extracellular Ca2+ (1.3 mM) was removed, a decrease in resting level and a small, transient increase in [Ca2+]i were observed. 5-HT stimulation also induced an increase in the production of inositol triphosphate. 5-HT-induced increase in [Ca2+]i was significantly, but partially inhibited by staurosporin and H-7. Phorbol 12-myristate 13-acetate induced an increase in [Ca2+]i, which was abolished by removal of extracellular Ca2+. 5-HT-induced increase in [Ca2+]i was not affected by the pretreatment with pertussis toxin (PTX), and was not accompanied by a change in cyclic AMP content. These results suggest that, in cultured rat aortic smooth muscle cells, 5-HT increases [Ca2+]i via 5-HT2 receptor subtype by inducing influx of extracellular Ca2+ partially through L-type voltage-dependent Ca2+ channel, as well as by mobilizing Ca2+ from its intracellular stores. Activation of protein kinase C may be positively involved in the regulatory mechanism of Ca2+ influx, but PTX-sensitive G protein and cyclic AMP seem to be not involved.
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PMID:Effect of 5-hydroxytryptamine on intracellular calcium dynamics in cultured rat vascular smooth muscle cells. 959 25

1. The modulatory effect of 5-hydroxytryptamine (5-HT) on the gamma-aminobutyric acid(A) (GABA(A)) response was investigated in the neurones freshly dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch recording configuration under the voltage-clamp conditions. 2. 5-HT potentiated GABA-induced Cl- current (IGABA) without affecting the reversal potential of IGABA and the apparent affinity of GABA to its receptor. 3. Alpha-Methyl-5-HT mimicked the potentiation effect of 5-HT on IGABA while ketanserine blocked it. 1-Oleoyl-2-acetyl-glycerol (OAG) potentiated IGABA, and the effect of 5-HT on IGABA was occluded by OAG pretreatment. In the presence of chelerythrine, 5-HT failed to potentiate IGABA, suggesting that protein kinase C (PKC) is involved in the pathway through which the activation of the 5-HT2 receptor potentiates the IGABA. 4. The facilitatory effect of 5-HT on IGABA remained in the presence of BAPTA-AM. LiCl also had no effect on 5-HT-induced potentiation of IGABA. 5. H-89, genistein, okadaic acid and pervanadate all had no effects on 5-HT potentiation of IGABA. Pertussis toxin treatment for 6-8 h did not block the facilitatory effect of 5-HT on IGABA. 6. The present results show that GABA(A) receptor in the rat SDCN could be modulated in situ by 5-HT, one of the major transmitters involved in the supraspinal control of nociception, and that the phosphorylation of GABA(A) receptor by PKC may be sufficient to support such modulation. The results also strongly support the hypothesis that the cotransmission by 5-HT and GABA has an important role in the spinal cord.
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PMID:5-HT potentiation of the GABA(A) response in the rat sacral dorsal commissural neurones. 969 Aug 71

Intracellular recordings were made from pyramidal neurons in layers V and VI of the rat medial prefrontal cortex in slice preparations to investigate the effect of the serotonin 5-HT2A,2C receptor agonist (-)-1-2,5-dimethoxy-4-bromophenol-2-aminopropane (DOB) and 5-hydroxytryptamine (5-HT) on N-methyl-D-aspartate (NMDA)-induced responses. Bath application of either DOB or 5-HT [in the presence of antagonists to 5-HT1A, 5-HT3 and gamma-aminobutytric acid (GABA) receptors] produced a concentration-dependent biphasic modulation of the NMDA responses. They facilitated and inhibited NMDA responses at low (</= 1 microM DOB and </= 50 microM 5-HT) and higher concentrations, respectively. Both the facilitating and inhibitory action were blocked by the highly selective 5-HT2A receptor antagonist R-(+)-alpha-(2, 3-dimethoxyphenil)-1-[4-fluorophenylethyl]-4-piperidineme thanol (M100907) and the 5-HT2 receptor antagonist ketanserin, thus indicating that both facilitation and inhibition were mediated by the activation of the 5-HT2A receptor subtype. However, the facilitating, but not inhibitory, action of DOB showed a marked desensitization, suggesting that the facilitation and inhibition of NMDA responses resulted from activation of different 5-HT2A receptor subtypes and/or signal-transduction pathways. Indeed, the selective PKC inhibitor chelerythrine and the Ca2+/CaM-KII inhibitor KN-93 prevented the facilitating and inhibitory action of DOB, respectively. We have generated several lines of evidence to indicate the following scenario. Low concentrations of DOB, at presynaptic nerve terminals, markedly enhance NMDA-induced release of excitatory amino acids (EAAs), which then act upon both NMDA and non-NMDA receptors to elicit inward current. The massive inward current masks the postsynaptic inhibitory action of DOB. At higher concentrations, DOB inhibits the release of EAAs and discloses the postsynaptic inhibitory action.
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PMID:A pre- and postsynaptic modulatory action of 5-HT and the 5-HT2A, 2C receptor agonist DOB on NMDA-evoked responses in the rat medial prefrontal cortex. 1045 88

The effects of 5-HT and NA on glycine-gated Cl- channel currents(IGly) and its intracellular mechanisms were investigated in acutely dissociated rat sacral dorsal commissural neurons by using nystatin perforated patch clamp recording. It was found that: (1) the activation of 5-HT2 receptor coupled to IAP-insensitive G-proteins increases intracellular DAG formation through the activation of phospholipase C(PLC). The accumulation of DAG increases the Ca(2+)-independent or novel PKC(nPKC) activity, resulting in the potentiation of IGly; (2) the activation of alpha 2-adrenoceptor by NA coupled to IAP-sensitive G-proteins reduces intracellular cAMP formation through the inhibition of adenylyl cyclase (AC). The reduction of cAMP decreases PKA activity, resulting in the potentiation of IGly.
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PMID:[Enhancement of glycine-gated Cl- channel currents by 5-HT and NA in rat sacral dorsal commissural neurons is mediated by protein kinases]. 1103 31

Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABA(A) and GABA(B) receptor antagonists. Bath application of 5-HT (10 microm) for 5-10 min increased the amplitude of the EPSP and EPSC. (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC. Alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 microm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 microm), selective 5-HT2B and 5-HT2C receptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 microm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10 microm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by alpha-methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 microm) and alpha-methyl-5-HT (10 microm) increased the frequency of miniature EPSPs (mEPSPs) without changing the mEPSP amplitude. The ratio of the paired pulse facilitation was significantly decreased by 5-HT and alpha-methyl-5-HT. The 5-HT-induced facilitation of the EPSP was blocked by calphostin C (100 nm), a specific protein kinase C (PKC) inhibitor, but not by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 microm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 microm) mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT2A receptors that link with PKC in rat DLSN neurons.
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PMID:Activation of presynaptic 5-hydroxytryptamine 2A receptors facilitates excitatory synaptic transmission via protein kinase C in the dorsolateral septal nucleus. 1219 74


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