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

The paper describes and compares the influences of the antidepressants (imipramine, mianserin, citalopram), electroconvulsive shock, and the neuroleptics (haloperidol, chlorpromazine and spiperone) on the systems of second messengers related to adrenergic receptors in rat cerebral cortex, measured by generation of cyclic AMP and inositol phosphate (IP), and their influence on the effects of activation of protein kinase C (PKC) by its synthetic activator, phorbol ester (TPA). The effect of PKC-stimulation was expressed as a reduction of noradrenaline-stimulated IP accumulation and, on the other hand, as an enhancement of cyclic AMP response under stimulation with noradrenaline and isoproterenol. When administered chronically, the described antidepressants (unlike the neuroleptics) augmented IP accumulation or left it unchanged, but they reduced PKC's negative feedback with the alpha 1-adrenoceptor. PKC-induced potentiation of cyclic AMP's response to beta-adrenergic receptor stimulation was unchanged or enhanced, while the antidepressants reduced the generation of this second messenger. However, citalopram increased cyclic AMP generation and reduced PKC potentiation. Taking into account the role of PKC in adrenergic receptors cross-talk explains why, despite antagonization of alpha 1-adrenoceptors and induction of beta down-regulation by some antidepressants, enhancement of the process of noradrenergic neurotransmission can occur as a final effect of the action of these drugs. It was found that the action of antidepressants is largely related to the adrenergic system, even when their action on this system is not direct and is accomplished by their influence on another neurotransmitting system, e.g. the serotonergic system.
Pol J Pharmacol
PMID:The effect of psychotropic drugs on the interaction of protein kinase C with second messenger systems in the rat cerebral cortex. 798 66

We tested how chronic antidepressant treatments (chronic imipramine, chronic electroconvulsive shock (ECS) and chronic ECS given after chronic imipramine) affect the feedback inhibition of alpha 1-adrenoceptor activity (measured with inositol phosphate (IP) accumulation after stimulation with noradrenaline). The inhibitory effect of a 12-O-tetradecanoylphorbol 13-acetate (TPA) on IP response was found to be due to protein kinase C (PKC) activation, as it was abolished by specific protein kinase inhibitors, staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Chronic ECS completely abolished the inhibition by TPA of inositol phosphate response to noradrenaline, while chronic imipramine reversed the feedback and led to potentiation of responses by TPA to intermediate concentrations of noradrenaline. Subsequent chronic ECS abolished the imipramine-induced reversal of TPA inhibition and lead to the changes similar as observed after ECS alone. The present results may suggest why in some cases, in which imipramine therapy is ineffective, subsequent ECS may be clinically beneficial.
Pol J Pharmacol
PMID:The antagonistic effect of separate and consecutive chronic treatment with imipramine and ECS on the inhibition of alpha 1-adrenoceptor activity by protein kinase C. 801 75

The aim of this study was to investigate the binding of chlorpromazine and haloperidol to rat cerebral cortical adrenoceptors and to assess their effect on responsiveness of alpha 1- and beta-adrenoceptors measured by accumulation of second messengers, inositol phosphate and cyclic AMP, after stimulation with noradrenaline and isoproterenol. The effect of neuroleptics on protein kinase C was assessed by carrying out incubations in the absence and presence of the phorbol ester, 12-O-tetradecanoyl-phorbol 13-acetate (TPA). The effects of chronic administration of haloperidol (0.5 mg/kg/d for 14 days) on responses of second messenger systems to noradrenaline and isoproterenol in the presence and absence of TPA were also measured. The results indicate that in vitro chlorpromazine and haloperidol similarly inhibit noradrenaline-induced responses of inositol phosphate and cyclic AMP, but differently affect the potentiation of these responses by protein kinase C: the inhibitory effect of haloperidol, but not that of chlorpromazine was prevented by TPA. Similarly, only chlorpromazine inhibited the cyclic AMP responses to isoproterenol. The differences between the effects of chlorpromazine and haloperidol may be explained by their different affinity to various subtypes of adrenoceptor. In a chronic experiment haloperidol did not induce changes in responsiveness of cortical alpha 1- and beta-adrenoceptors, but inhibited TPA-induced potentiation of cyclic AMP responses.
Pol J Pharmacol
PMID:The effects of chlorpromazine and haloperidol on second messenger systems related to adrenergic receptors. 811 83

Feline immunodeficiency virus (FIV) is a member of the genus Lentivirus of the family Retroviridae. FIV can infect T lymphocytes and monocytes/macrophages in vitro and in vivo, and causes an acquired immunodeficiency syndrome-like disease in cats. Several isolates of FIV from geographically distant countries have been molecularly cloned. There is considerable heterogeneity especially in Env gene among the FIV isolates and they can be divided into two or more subgroups. Like other lentiviruses, FIV has a complex genome structure. Gag gene encodes matrix, capsid and nucleocapsid proteins, and Pol gene encodes protease, reverse transcriptase, dUTPase and integrase. The dUTPase is not present in the primate lentiviruses but present in the non-primate lentiviruses. Env gene encodes surface and transmembrane envelope glycoproteins. In addition to the structural and enzymatic proteins, at least three more genes (Vif, ORF A, Rev) are present in FIV. Vif is related to the infectivity of the cell-free viruses. Rev functions in the stability and transport of incompletely spliced viral RNAs from the nucleus to cytoplasm and is indispensable for virus replication. Although the Tat protein of the primate lentiviruses is essential for virus replication, ORF A (putative Tat gene) of FIV is not essential for virus replication in established feline T lymphoblastoid cell lines. However, the ORF A gene product is related to the efficient replication of the virus in primary peripheral blood lymphocytes. In the long terminal repeat (LTR) of FIV, there are many putative binding sites for enhancer/promoter proteins. Among these binding sites, the putative AP-1 site is important for basal promoter activity of the LTR and responsible for the T cell activation signal through protein kinase C, however the site is not required for the virus replication in established feline T lymphoblastoid cell lines. Comparative study of the molecular biology of lentiviruses revealed that the genome structure, splicing pattern and functional enhancer protein-binding sites of FIV are more similar to those of the ruminant lentiviruses than those of the primate lentiviruses.
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PMID:The genome of feline immunodeficiency virus. 812 13

Lipopolysaccharide (LPS) and phorbol esters (TPA) stimulate lymphocytes proliferation in two different ways. While LPS primary function is specific receptor binding, TPA directly activate cellular protein kinase C. The stimulation of human leukaemic lymphocytes (from chronic lymphocytic leukaemia patients) with LPS and TPA results in two different types of response: to both stimulators, and to LPS only. Therefore the supposed defect of cellular receptors can not explain all the observed effects. The existence of TPA independent second messengers and changes in signal transduction pathways downstream of PKC can be considered.
Acta Haematol Pol 1993
PMID:[In vitro studies directed at inducing differentiation of leukemic B-lymphocytes]. 830 80

The aim of this study was to compare the mechanisms of increased responsiveness of the beta-adrenoceptor dependent cyclic AMP generating system induced by chronic decrease of noradrenaline availability (beta-upregulation) with that resulting from simultaneous stimulation of alpha-adrenoceptors (alpha-potentiation) and to assess the role of protein kinase C in these phenomena. The beta-upregulation was produced by central chemosympathectomy with 6-hydroxydopamine. The role of alpha 1- and alpha 2-adrenoceptors was assessed by comparison of the effects of specific beta-adrenoceptor agonist isoproterenol with those of a mixed alpha-beta-adrenoceptor agonist noradrenaline, and clonidine was used to selectively stimulate alpha 2-adrenoceptors. The role of protein kinase C was assessed by measuring cyclic AMP responses in the presence and absence of 12-O-tetradecanoyl-phorbol 13-acetate. The results indicate that the mechanism of increased responsiveness induced by central chemosympathectomy is different from the alpha-potentiation, that only alpha 1-adrenoceptors are involved positively in alpha-potentiation, while the alpha 2-adrenoceptors play an inhibitory role, and that increased responsiveness following central chemosympathectomy may be inhibited by protein kinase C activation.
Pol J Pharmacol
PMID:Phorbol ester and central chemosympathectomy augment beta-adrenoceptor response by different mechanisms. 840 69

B-50/GAP-43 is a growth-associated phosphoprotein enriched in growth cones and in the presynaptic terminal. The expression of the protein is restricted to the nervous system and is highest in the first week after birth. In adult brain, B-50 is enriched in areas with high plasticity. The regulation of expression of the B-50 gene occurs both at the transcriptional and post-transcriptional level by unknown mechanisms. The gene contains 2 regions displaying promoter activity, the most 3' of which (P2) is the active on in vivo. Expression of B-50 in non-neuronal cells results in filopodial extensions whereas antibodies or antisense oligo's to B-50 prevent neurite outgrowth. The protein is important for neuronal pathfinding. Several post-translational modifications have been described, ADP-ribosylation and palmitoylation in the membrane binding domain, phosphorylation by PKC, casein kinase II and phosphorylase kinase, and dephosphorylation by several phosphatases, among which is calcineurin. Interactions of B-50 have been described with calmodulin, PIP kinase, F-actin, and phospholipids. Recent studies indicate that the phosphorylation state and amount of calmodulin bound to B-50 regulate the rate of transmitter release. Induction of long-term potentiation by high frequency stimulation of hippocampal slices results in an increased state of B-50 phosphorylation. This will increase the amount of free calmodulin in the presynaptic terminal and increase the amount of transmitter released. Although B-50 is involved in seemingly unrelated forms of neuronal plasticity, neurite outgrowth and transmitter release, our unifying hypothesis is that the protein plays an (unknown) essential, modulatory role in membrane expansion.
Acta Biochim Pol 1996
PMID:Presynaptic phosphoprotein B-50/GAP-43 in neuronal and synaptic plasticity. 886 78

To test how previous treatment with imipramine affects the action of electroconvulsive shock (ECS) on cortical beta-adrenergic system, male Wistar rats received imipramine, 10 mg/kg b.i.d. for two weeks, followed by 8 days of ECS, and 24 h after the last shock the responsiveness of beta-adrenoceptor system was tested by measuring cyclic AMP formation in cortical slices after exposure to noradrenaline or isoproterenol. To assess the possible role of protein kinase C, the same responses were measured in the presence of a protein kinase C activator, 12-O-tetradecanoyl-phorbol 13-acetate (TPA). ECS alone was found more effective in inducing beta-adrenergic-down-regulation than imipramine, and tended to produce stronger effect when given after chronic imipramine. In contrast to imipramine, which effectively inhibited TPA-induced potentiation of the action of isoproterenol, ECS strongly facilitated it. However, administrated after chronic treatment with imipramine, ECS did not change the potentiation. The results suggest that effects of ECS are slightly modified, but not inhibited by previous administration of imipramine.
Pol J Pharmacol
PMID:Modulation of electroconvulsive treatment induced beta-adrenergic down-regulation by previous chronic imipramine administration: the involvement of protein kinase C. 911 90

In membrane preparation of chick cerebral cortex, HA (histamine) did not affect both basal and forskolin-stimulated adenylyl cyclase activity. However, in slices of chick cerebral cortex prelabeled with [3H]adenine, HA, as well as 2-methylHA, 4-methylHA, and N alpha-methylHA, potently increased [3H]cyclic AMP accumulation in a concentration-dependent manner. The stimulatory effect of the HA-ergic compounds on cyclic AMP formation was antagonized by HA H2-receptor blockers (aminopotentidine, ranitidine), and by chelerythrine (50 microM), a potent and selective inhibitor of PKC (protein kinase C). Of the two other tested PKC inhibitors H-7 (100 microM) significantly reduced the HA action, while the effect of staurosporine (1 microM) did not reach the level of statistical significance. Preincubation of chick cerebral cortical slices with a PKC activator, PDB (4 beta-phorbol 12,13-dibutyrate, 1 microM), markedly enhanced the accumulation of cyclic AMP evoked by HA, 2-methylHA, 4-methylHA and N alpha-methylHA. 4 beta-Phorbol, inactive on PKC, was ineffective. A possible role of PKC in the regulation of HA-induced cyclic AMP synthesis in chick cerebrum has been discussed.
Pol J Pharmacol
PMID:Effects of substances affecting protein kinase C on histamine-evoked stimulation of cyclic AMP formation in chick cerebral cortex. 911 98

Two isoforms of sucrose synthase (SS1 and SS2) from maize (Zea mays, var. Mona) seedlings co-purified with a calcium and phospholipid dependent protein kinase. The enzymatic preparation obtained gave a positive reaction with the antibody against mammalian protein kinase C. Maize sucrose synthase was phosphorylated by the endogenous protein kinase. Also, mammalian protein kinases (protein kinase C and protein kinase A) were able to phosphorylate the 86 kDa subunit of sucrose synthase. When excised seedlings were fed [32P]orthophosphate, sucrose synthase was also phosphorylated. Microsequencing of in vivo labelled enzyme has shown phosphorylation of Ser-15 in SS2. The present work provides evidence that maize sucrose synthase is the physiological substrate of the endogenous calcium and phospholipid dependent protein kinase(s).
Acta Biochim Pol 1997
PMID:Phosphorylation of sucrose synthase from maize seedlings. 958 64


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