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

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four hundred and thirty blood samples from suxamethonium-sensitive individuals have been phenotyped by the Cholinesterase Research Unit following its transfer from Exeter to the Hammersmith Hospital. The distribution of genotypes has been shown to be similar to that found in Exeter. Screening for the Elk and Elj genes has not yielded any major differences in the gene frequencies of sensitive individuals, even during pregnancy. The uneven sex distribution of the patients, as well as other unusual points that have arisen, are discussed. A new gene for the biosynthesis of cholinesterase has probably been identified.
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PMID:Phenotyping of individuals sensitive to suxamethonium. The Cholinesterase Research Unit at the Royal Postgraduate Medical School. 365 Dec 74

Neutral endopeptidase 24.11 (NEP; "enkephalinase") may inactivate a number of centrally active neuropeptides including the enkephalins and substance P. In most areas of the central nervous system, the cell types which express NEP activity are not known. The hypoglossal nucleus (N.XII) was selected as a model system to characterize the cytochemical localization of NEP. The effect of hypoglossal nerve axotomy upon the distribution of NEP activity in the hypoglossal nucleus was compared to the effect upon cholinergic markers, the mu opiate receptor, and the enkephalins. By use of a fluorescence histochemical method, NEP was localized at all levels of N.XII to the soma and proximal processes of the majority of the apparent motor neurons in the nucleus. Fluorescent double-labeling studies revealed the presence of numerous enkephalinergic varicosities which localized to the neuropil surrounding NEP-stained motor neurons. To determine whether NEP was synthesized by these motor neurons, 18 rats received a unilateral transection of the hypoglossal nerve. A pronounced decrease in NEP staining in N.XII was observed on the operated side as early as 3 days following axotomy. This decrease persisted at all levels of the nucleus for about 5 weeks. By 7 weeks, the staining between the control and operated sides was indistinguishable. By contrast, there was no apparent change in the density or distribution of enkephalin-immunoreactive varicosities in five animals examined 6 to 32 days following axotomy. Radioligand binding of [3H]DAMGO to the mu-opiate receptor in N.XII was studied in 20 animals by quantitative autoradiography at 2, 6, and 11 days after axotomy. No significant changes in the level of radioligand binding to the mu-receptor were detected in response to axotomy. In contrast to the opiate system, the cholinergic enzymes choline acetyltransferase, acetylcholinesterase, and pseudocholinesterase showed a coordinate decrease in motor neuron-associated staining on the operated side of N.XII at 3, 6, and 11 days following axotomy which paralleled the decrease in NEP staining. By contrast, the lysosomal enzyme marker, acid phosphatase, showed a pronounced increase in staining on the operated side. The results of this study are consistent with the synthesis of NEP by cholinergic N.XII motor neurons and indicates that the enkephalins and NEP in N.XII are closely associated, but derive from separate neuronal populations. The widespread overlap in the distribution of NEP-stained motor neurons and enkephalinergic varicosities in N.XII provides additional anatomical support for a potential role for NEP in the inactivation of centrally active enkephalins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential response of neutral endopeptidase 24.11 ("enkephalinase"), and cholinergic and opioidergic markers to hypoglossal axotomy. 820 Oct 16

Because of the low basal output, measurement of acetylcholine (ACh) release from enteric neurons usually requires cholinesterase inhibition, a condition which is known to interfere with feed-back mechanisms regulating ACh release. In this study, we resorted to a highly sensitive HPLC-ED method to determine the minimum requirement of physostigmine to achieve reliable quantitation of spontaneous endogenous ACh overflow from the guinea-pig isolated colon. Furthermore, in order to assess the degree of interference by physostigmine with cholinergic function, we assessed the effect of scopolamine and oxotremorine (in the presence of physostigmine) on spontaneous ACH overflow (to detect the presence of autoreceptors) and also measured the efficiency of the peristaltic reflex with different physostigmine concentrations. Spontaneous endogenous ACh overflow was detectable only with physostigmine concentrations > or = 10 nM. ACh overflow increased with increasing physostigmine concentrations (10 nM-10 microM range). Scopolamine significantly enhanced the facilitatory effect of physostigmine concentrations > or = 10 nM; conversely, oxotremorine inhibited ACh overflow. Peristaltic efficiency was not significantly affected by physostigmine concentrations < or = 300 nM. In conclusion, this modified HPLC-ED method allows ACh detection with minimal physostigmine concentrations (10-30 nM), which do not interfere with peristaltic activity, do not saturate autoreceptor feed-back mechanisms and therefore improve the assessment of cholinergic function in colonic enteric neurons.
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PMID:Acetylcholine detection by a modified HPLC-ED method improves the assessment of cholinergic function in the myenteric plexus of the guinea-pig colon. 929 79

The effects of single intraperitoneal injection of two cholinesterase inhibitors, physostigmine (PHY; 0.01, 0.025, 0.05, 0. 1, 0.2 mg/kg) and heptylphysostigmine (HEP; 0.5, 2, 6 mg/kg) on electroencephalographic (EEG) activity and flash visual evoked potentials (f-VEP) in the occipital cortex were compared in DBA/2 mice. EEG spectral analysis of awake periods showed that PHY at all doses and HEP at 2 mg/kg induced an increase of power in the 4.25- to 7-Hz frequency band. Furthermore, PHY at the higher doses and HEP at all doses induced a decrease of power in the 7.25- to 12-Hz frequency band, while the lower doses of PHY (0.01, 0.025 mg/kg) produced an increase of this band. EEG effects elicited by the two drugs were similar, when doses displaying analogous biochemical effects (acetylcholinesterase inhibition) were used (i.e. 0.01 and 0. 025 mg/kg of PHY versus 0.5 and 2 mg/kg of HEP). PHY and HEP induced similar changes in f-VEPs. Amplitudes of early and late components (P1N1, N1P2, P4N4 and particularly N1P3) were enhanced, while amplitudes of middle components were depressed after all doses. The peak latency measures were generally delayed, even though, after the lower doses, a trend to a latency reduction was evident in late components. This finding might indicate a possible effect on stimulus speed diffusion by 'low therapeutic' doses, analogous to the ones used in men. Our data show that both drugs are effective in modifying EEG and f-VEP parameters connected with brain cholinergic function, although in a very narrow dose range.
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PMID:Effects of cholinergic drugs on neocortical EEG and flash-visual evoked potentials in the mouse. 1042 Jan 1

In the course of examining the actions of major human bile acids on cholinergic receptors, we discovered that conjugates of lithocholic acid are partial muscarinic agonists. In the present communication, we report that conjugates of deoxycholic acid (DC) act as cholinergic muscarinic receptor antagonists. Chinese hamster ovary (CHO) cells expressing rat M3-muscarinic receptors were used to test bile acids for inhibition of radioligand [N- (3)H-methylscopolamine ((3)H-NMS)] binding; alteration of inositol phosphate (IP) formation; mitogen-activated protein (MAP) kinase phosphorylation and cell toxicity. We observed approximately 18.8, 30.3 and 37.1% inhibition of (3)H-NMS binding with DC and its glycine (DCG) and taurine (DCT) conjugates, respectively (all 100 micromol/l, p < 0.01). DCT and DCG inhibited acetylcholine-induced increases in IP formation and MAP kinase phosphorylation (p44 and p42 ERK). DCG and DCT did not alter trypan blue exclusion or lactate dehydrogenase release from CHO-M3 cells. We observed the following rank order of potency (IC(50) micromol/l) for inhibition of (3)H-NMS by muscarinic antagonists and bile acids: NMS (0.0004) > 4-DAMP (0.009) > atropine (0.012) > DCT (170) > DCG (250). None of the bile acids tested were hydrolyzed by recombinant cholinesterase. At concentrations achieved in human bile, DC derivatives are natural muscarinic antagonists.
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PMID:Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists. 1211 52

Brain insulin receptor and ERK I/II are suggested to play a role in memory formation. We designed a series of experiments to explore if Asiasari radix (AR) extracts could display memory enhancing actions possibly via the activation of insulin receptor and ERK I/II in mice and rats. Methanol extract of AR had significantly increased survival time in the NaNO(2) intoxication assay in mice. Methanol extract of Asiasari radix (fraction 1) and its subfractions, chloroform-soluble fraction (fraction 2) and chloroform-insoluble, methanol-soluble fraction (fraction 4) were further tested for memory formation. In eight-arm radial maze experiments, both reference memory errors and working memory errors were significantly decreased in mice by fractions 1, 2 and 4. In addition, these fractions were also effective in promoting memory in the passive avoidance test in mice and rats. To gain insight into the mechanism of memory enhancing effects by Asiasari radix extracts, the activities of hippocampal insulin receptors and ERK I/II were tested in mice and rats. Fraction 1 significantly stimulated tyrosine phosphorylation of the insulin receptor, whereas ERK I/II were stimulated by fractions 1, 2 and 4. These fractions also inhibited cholinesterase activities in rats. These results suggest that Asiasari radix extracts may exert memory enhancing effects via activation of insulin receptor and ERK I/II as well as decreasing cholinesterase activity.
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PMID:Memory enhancing actions of Asiasari radix extracts via activation of insulin receptor and extracellular signal regulated kinase (ERK) I/II in rat hippocampus. 1274 37

Our previous studies have revealed the involvement of signaling pathways of BDNF and NT-4/5 via TrkB in the development, regeneration, survival and maintenance of the Ruffini endings, primary mechanoreceptors in the periodontal ligament. However, the involvement of other neurotrophins remains unclear. The present study examined the expression of GDNF, GFRalpha1, and RET in the incisor periodontal ligament and trigeminal ganglion of young rats by RT-PCR and immunocytochemistry. All these mRNAs were detected in both tissues by RT-PCR. These immunoreactions were found in the terminal Schwann cells associated with the periodontal Ruffini endings, as confirmed by histochemistry for non-specific cholinesterase activity. Their axonal branches showed GFRalpha1- and RET-immunoreactions but lacked GDNF-immunoreactivity. In the trigeminal ganglion, about 30% of the neurons were immunoreactive to GFRalpha1 and RET. Averages of cross-sectional areas of their positive neurons demonstrated that they could mainly be categorized as medium-sized neurons. GDNF-immunoreaction was restricted to the satellite cells and not in trigeminal ganglion neurons. These findings indicate that GDNF mediates trophic effects on the survival and target innervation of the periodontal Ruffini endings via GFRalpha1 and RET.
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PMID:Expression of GDNF and its receptors in the periodontal mechanoreceptor. 1651 66

Environmental substances seem to be involved in the etiology of breast cancers. Many studies have found an association between human cancer and exposure to agricultural pesticides such as the organophosphorous pesticides. Parathion is a cholinesterase inhibitor that induces the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. The primary target of action in insects is the nervous system whereby pesticides inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Atropine is a parasympatholytic alkaloid used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to determine the effect of parathion and atropine on cell transformation of human breast epithelial cells in vitro. These studies showed that parathion alone was able to induce malignant transformation of an immortalized human breast epithelial cell line, MCF-10F as indicated by increased cell proliferation, anchorage independency and invasive capabilities. There was also an increase in c-kit, Trio, Rho-A, Rac-3, EGFR, Notch-4, Dvl-2, Ezrin, beta catenin and mutant p53 protein expression in the parathion-treated cells. However, atropine significantly inhibited this increase. In a human cell cycle array of 96 genes, 13 of them were altered by parathion treatment. Among the genes affected were the cyclins, such as cyclin D3, the cyclin-dependent kinases (CDKs) such as CDK41 and the minichromosome maintenance deficient (MCM) MCM2 and MCM3. It is suggested that parathion influences human breast epithelial cell transformation and is an initiator factor in the transformation process in breast cancer.
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PMID:Gene expression signature of parathion-transformed human breast epithelial cells. 1739 78

The brain insulin receptor and ERK I/II are known to play an important role in memory formation and neuroprotection. A series of experiments was designed to explore if Liriopsis tuber (LT) extracts could exhibit neuroprotection and memory enhancing actions. LT was extracted with 70% methanol and subsequently fractionated into chloroform (fraction C), chloroform/methanol-(3:1) (fraction CM), methanol-soluble (fraction M) and methanol-insoluble, water-soluble fractions (fraction A). The LT fractions (T, C, M, A) significantly inhibited the cortical depolarization induced by AMPA in cortical slices of rats. In addition, these fractions were also effective in promoting memory in the passive avoidance test in mice. To gain insight into the mechanism of memory enhancing effects by Liriopsis tuber extracts, the activities of hippocampal insulin receptors and ERK I/II were tested in rats. Extract of LT (T) dramatically stimulated tyrosine phosphorylation of the insulin receptor, while fraction C of LT also significantly stimulated the same. In addition, ERK I/II were stimulated and cholinesterase activities were inhibited by fractions T, C, M and A in the rat hippocampus. These results suggest that Liriopsis tuber extracts may exert neuroprotection and memory enhancing effects via activation of the insulin receptor and ERK I/II as well as inhibiting cholinesterase.
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PMID:Extracts of Liriopsis tuber protect AMPA induced brain damage and improve memory with the activation of insulin receptor and ERK I/II. 1880 26

Natural flavonoids ameliorate amyloid-beta peptide (Abeta)-induced neurotoxicity. We examined whether the fustin flavonoid affects Abeta-induced learning impairment in mice. Repeated treatment with fustin significantly attenuated Abeta (1-42)-induced conditioned fear and passive avoidance behaviors. This effect was comparable to that of EGb761, a standard extract of ginkgo. Fustin treatment significantly prevented decreases in acetylcholine (ACh) levels, choline acetyltransferase (ChAT) activity, and ChAT gene expression induced by Abeta (1-42). Fustin also consistently suppressed increases in acetyl cholinesterase (AChE) activity and AChE gene expression induced by Abeta (1-42). In addition, fustin significantly attenuated Abeta (1-42)-induced selective decreases in muscarinic M1 receptor gene expression and muscarinic M1 receptor binding activity (as determined by [(3)H]pirenzepine binding) by modulating extracellular signal-regulated kinase 1/2 (ERK 1/2) and cAMP response-element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. These effects of fustin were reversed by treatment with dicyclomine, a muscarinic M1 receptor antagonist, and SL327, a selective ERK inhibitor, but not by chelerythrine, a pan-protein kinase C (PKC) inhibitor. Taken together, our results suggest that fustin attenuates Abeta (1-42)-impaired learning, and that the ERK/CREB/BDNF pathway is important for the M1 receptor-mediated cognition-enhancing effects of fustin.
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PMID:Fustin flavonoid attenuates beta-amyloid (1-42)-induced learning impairment. 1953 34


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