Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with atopic dermatitis have abnormal autonomic responses of the arterioles, pilomotor smooth muscle, and sweat glands. Their lesions have been reported to contain increased amounts of the neurohumors, acetylcholine and norepinephrine, as well as increased activity of acetylcholinesterase and catechol-O-methyltransferase. In vitro studies of epidermis show that beta adrenergic agonists fail to evoke the normal inhibition of mitosis of basal cells of patients with atopic dermatitis. Epidermis removed not only from the lesions, but also from normal-appearing skin, responded abnormally. The increase in intracellular levels of cAMP after exposure to catecholamines was similar in normal and atopic epidermis. Lymphocytes and PMN leukocytes isolated from patients with atopic dermatitis show both a decreased physiologic response (glycogenolysis and inhibition of lysosome enzyme release) and a decreased rise in intracellular levels of cAMP upon incubation with beta agonists, but a normal response to PGE1. Cortisol increases the response of lymphocyte adenyl cyclase to both agonists and, in the case of the patients with atopic disease, more than overcomes the depressed response to beta agonists. Because the leukocytes respond normally to PGE1 and because others have reported normal activities of skin and adenyl cyclase, phosphodiesterase, and protein kinases, we conclude that the step responsible for the diminished beta adrenergic response lies antecedent to the catalytic site of adenyl cyclase.
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PMID:Adrenergic mechanisms and the adenyl cyclase system in atopic dermatitis. 0 56

The effects of an organophosphate (OP) pesticide, fenthion (FEN), on the release and metabolism of dopamine were evaluated in a clonal line of rat pheochromocytoma (PC12) cells. HPLC was used to determine media concentrations of DA and the DA metabolites norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). The FEN formulation solvent did not significantly affect DA metabolism. In the first study, cultures were treated with 10(-5) or 10(-6) M FEN or 10(-5) M neostigmine, a non-OP acetylcholinesterase inhibitor. Concentrations of both catecholamines were elevated in cultures treated with 10(-5) M FEN by 2.8-fold for DA and 3.5-fold for NE. Neostigmine effects were of smaller magnitude and DA was decreased after 24 hr. Cultures were also treated with depolarizing levels of K+, but the effect of FEN was not altered, suggesting that FEN does not act by increasing DA release. In the second study, the effect of 10(-6) M FEN was evaluated in cultures treated with the DA uptake inhibitor benztropine, the monoamine oxidase (MAO) inhibitor pargyline, or the catechol-O-methyltransferase (COMT) inhibitor tropolone. Inhibitor effects were consistent with their known mechanisms of action. In all cultures treated with FEN, the ratio HVA/DOPAC was decreased after 3 and 6 hr of exposure. A decrease in HVA/DOPAC was also observed in cultures treated with neostigmine and tropolone. In combination with pargyline, FEN decreased DA in contrast to its usual effect of increasing DA. Neither the stimulation of DA release nor the inhibition of DA uptake affected the observed action of FEN in PC12 cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release and metabolism of dopamine in a clonal line of pheochromocytoma (PC12) cells exposed to fenthion. 261 80

The slow inhibitory postsynaptic potential (slow IPSP), the slow excitatory postsynaptic potential (slow EPSP), the late slow excitatory postsynaptic potential (late slow EPSP), and the fast excitatory postsynaptic potential/compound action potential (fast EPSP) were recorded from the 9th or 10th paravertebral sympathetic ganglia of bullfrogs (and some Rana pipiens frogs) by the sucrose-gap technique. The adrenergic antagonists phentolamine, dihydroergotamine and propranolol did not show any antagonistic effect on the slow IPSP when used at concentrations of up to 10, 100 and 10 microM, respectively. U-0521 (3',4'-dihydroxy-2-methylpropriophenone, 50 micrograms/ml), a specific inhibitor of catechol-O-methyltransferase, did not show any potentiating effect on the slow IPSP. The cholinesterase inhibitor neostigmine (0.5-1 microM) induced a large increase in the duration and amplitude of slow IPSP. When phentolamine and propranolol at concentrations greater than 10 microM were used the slow IPSP (and all other synaptic potentials) were non-specifically reduced in amplitude by these drugs. The results reported in this paper do not lend any support to the hypothesis that the slow IPSP in frog sympathetic ganglia is mediated by an adrenergic interneuron. The results are consistent with the proposal that the slow IPSP in this ganglion is mediated by a direct action of acetylcholine released from cholinergic preganglionic fibers.
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PMID:Pharmacological studies in frog sympathetic ganglion: support for the cholinergic monosynaptic hypothesis for slow IPSP mediation. 326 Nov 94

Brain capillaries (microvessels) were isolated from rabbit brain. Morphological characterization revealed relatively pure fractions of microvessels consisting of the capillary endothelium, the basal membrane, and the pericyte. These fractions of brain capillaries show acetylcholinesterase (AChE) and monoamine oxidase (MAO) activity, but lack catechol-O-methyltransferase and GABA transaminase activity. Isolated brain capillaries together with samples of the brain parenchyma and serum were used to study the role of AChE present in the brain capillary wall in soman intoxication. The results showed this AChE to be less sensitive to soman inhibition than AChE of brain parenchyma. Serum and brain AChE recovered to some extent in soman-intoxicated rabbits given HI-6, whereas AChE present in the microvessel was even further inhibited. It is suggested that soman-induced vasospasm in rabbit brain may explain both the inaccessibility of capillary AChE to soman and also the unfavorable effect of HI-6 on this enzyme.
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PMID:Soman intoxication and the blood-brain barrier. 409 83

The kinetic parameters of monoamine oxidase (MAO; E.C 1.4.3.4) and catechol-O-methyltransferase (COMT; EC 2.1.1.6) were evaluated in extracts of adrenergic and non-adrenergic mouse neuroblastoma cells and in rat glioma cells. Using the naturally-occurring substrates tyramine, tryptamine, serotonin and norepinephrine, the affinity of MAO for a given substrate was independent of the presence of the catecholaminergic pathway or cell type used, with apparent Km values ranging from 8-14 microM for tryptamine to 510-580 microM for norepinephrine. The MAO activity in glioma cells was substantially greater than in either neuroblastoma clone, but Vmax values varied little with substrate among cell lines. Both the neuronal and glial COMT had a similar Km for 1-norepinephrine (200 microM); the corresponding Vmax values were also similar among the different cell lines, but represented only 2-10% of the maximal MAO activity. Neuroblastoma and glioma cells, when grown from early logarithmic to stationary phase, showed no significant changes in specific activity of either MAO or COMT. Growth of cells for 3 days with 1 mM-N6,O2'-dibutyryl adenosine-3',5'-cyclic monophosphate resulted in no marked change in either MAO or COMT activity. These results suggest that in neurons neither MAO nor COMT plays a major role in the type of transmitter inactivation that is analogous to that of acetylcholinesterase in cholinergic synapses. The occurrence of considerable MAO and acetylcholinesterase activities in glioma cells may indicate a role for these cells in neurotransmitter inactivation.
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PMID:Metabolism of biogenic amines in neuroblastoma and glioma cells in culture. 1217 May 89