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

S.c. injections of cholinergic agents, carbachol, methacholine and bethanechol, into fasted rats caused rapid increases in the plasma concentration of cyclic GMP, with a sharp peak at 5--10 min after the injection. Acetylcholine gave rise to a rapid accumulation of cyclic GMP in plasma only when administered together with physostigmine which produced only a slight, if any, potentiation of the action of the cholinesterase-resistant choline esters. Cyclic AMP also increased after these drugs, but only subsequently to the rise of cyclic GMP; the primary action of the cholinergic drugs appeared to be the increase in cyclic GMP. Atropine was effective not only in abolishing the increase in plasma cyclic GMP induced by cholinergic drugs but also in lowering the baseline level of cyclic GMP. It was concluded that the plasma concentration of cyclic GMP could serve as a good parameter of cholinergic activity in rats.
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PMID:Plasma cyclic GMP: response to cholinergic agents. 2 43

A variety of compounds were assessed for their ability to induce morphological differentiation and to affect the synthesis of RNA in uncloned mouse neuroblastoma cells in culture. The stimulation of morphological differentiation in uncloned cells after exposure for 48 hours to concentrations of 3 times 10-7 to 3 times 10-4 M papavarine or 10-9 to 10-3 M dibutyryl adenosine 3':5'-monophosphate (dibutyryl-cAMP) was associated, in part, with a concentration-dependent decrease in incorporation of [5-3H]uridine into ribosomal RNA (rRNA) and heterogeneous RNA (HnRNA). The latter effect on cellular RNA produced by papavarine occurred within 1 hour after its addition to the medium and was associated with impaired uptake of radioactive precursor into uridine nucleotides and reduction in the intracellular concentration of uridine 5'-triphosphate (UTP). Dibutytyl-cAMP produced a decreased in the specific radioactivity of UTP without affecting the concentration of UTP in the tumor cells. The effects of papavarine and dibutyryl-cAMP could be distinguished further by the 50% reduction of acetylcholinesterase activity produced by papavarine, but not by dibutyryl-cAMP. Papavarine did not, however, reduce the cellular level of the soluble enzyme, adenine phosphoribosyltransferase. Sodium butyrate, while producing morphological effects similar to those of papavarine and dibutyryl-cAMP at equimolar concentrations, caused no significant changes in the incorporation of [5-3H]uridine into rRNA and HnRNA; however, acetylcholinesterase activity was stimulated 6- to 7-fold above control levels. In contrast to the other differentiating agents examined, addition of 10-9 to 3 times 10-4 M concentrations of cAMP to the tissue culture medium enhanced morphological differentiation of nueroblastoma cells, and caused a 10- to 20-fold stimulation of the incorporation of [5-3H]uridine into rRNA and HnRNA at concentrations of 10-4 M and higher. This effect observed only at high concentrations of cyclic nucleotide was accompanied by an elevation in the specific acitivty of UTP, These studies suggest that the morphological response of neuroblastoma cells is not necessarily associated with concomitant alterations in the synthesis of RNA with agents other than cAMP. Observed changes in incorporation of [5-3H]uridine into RNA appear in most instances to be due to alterations in the uptake of uridine, and in the pool size and specific radioactivity of UTP.
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PMID:Effects of adenosine 3':5'-monophosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture. 16 51

Organophosphate poisoning with malathion caused large increases (up to 125 and 440%, respectively) in the level of cyclic GMP in larvae of Mamestra configurata Wlk. and in the fly Sarcophaga bullata Parker. Cyclic AMP was little affected. The malathion-induced increase in cyclic GMP was time and dose dependent. Time-course studies with the head and thorax of S. bullata demonstrated that the increase in cyclic GMP level occurred precipitously after a lag period of about 1 h, during which time the activity of acetylcholinesterase (EC 3.1.1.7) was progressively inhibited. The abrupt increase in cyclic GMP began when acetylcholinesterase activity had been inhibited to a sufficient extent to permit accumulation of acetylcholine. It is suggested that the accumulation of acetylcholine in the malathion-poisoned insects caused cyclic GMP levels to rise. Cyclic GMP may have a role in cholinergic transmission in normally functioning insect neural tissue. Increased levels of cyclic GMP induced by organophosphate and organocholorine (Bodnaryk, R. P. (1976) Can. J. Biochem. 54, 957-962) insecticides appear to be a vital and previously unrecognized biochemical lesion in insects poisoned by these compounds.
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PMID:Correlation between organophosphate poisoning, acetylcholinesterase inhibition, and increased cyclic GMP levels in malathion-treated insects. 19 84

The paper describes adenosine effects on the acetylcholine synthesis and the profiles of adenine nucleotides, adenosine, inosine, and hypoxanthine in the rat brain in vivo after intracerebral (intraventricular) and intraperitoneal administration of adenosine. Intracerebral as well as extracerebral adenosine injection caused a dose- and time-dependent increase of the cerebral acetylcholine level, which was not accompanied by an equal development of the contents of adenine compounds and their degradation products. However, a considerable turnover of adenosine was observed in the brain after both routes of administration concerning the nucleotide as well as the degradation pathway. The kinetics of the purified enzymes of choline acetyltransferase and acetylcholinesterase were not influenced by adenosine. By this, the adenosine-caused increase of the cerebral acetylcholine cannot be explained by a direct molecular attack of adenosine on the enzymes of the synthesis or degradation of acetylcholine. An indirect mechanism which includes cAMP was discussed as a possible interpretation at present.
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PMID:Brain acetylcholine, adenine nucleotides and their degradation products after intraperitoneal and intracerebral adenosine administration. 20 36

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman were investigated on different receptors coupled to phosphoinositide (PPI) breakdown on hippocampal slices in vitro. We observed that muscarinic receptor subtypes M1 and M3 are involved in the increase of intracellular inositol phosphate, which is consistent with the procholinergic effect of soman induced by inhibition of AChE. Although the M2 receptor subtypes are known to be coupled to the cAMP second messenger, we demonstrated that in vitro, under soman, they are also involved in the PPI turnover. The other receptor subtypes known to be linked to PPI hydrolysis are not involved in this model of stimulation.
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PMID:Soman-induced phosphoinositide hydrolysis in rat hippocampal slices: biochemical characterization. 133 1

In an attempt to investigate the role of cAMP-dependent phosphorylations on synaptic transmission at an Aplysia cholinergic buccal ganglion synapse, the effects of xanthine derivatives such as 3-isobutyl-1-methylxanthine (IBMX), which is well known to inhibit phosphodiesterase activity thereby promoting cAMP accumulation, and a novel xanthine derivative, S-9977-2 were evaluated. They were found to potentiate cholinergic transmission by significantly increasing the time constant of decay (Tc) of inhibitory postsynaptic currents (IPSCs). The postsynaptic origin of the phenomenon was supported by the observation that responses to the ionophoretic application of acetylcholine (ACh) were also potentiated in duration as well as in amplitude. No effects of S-9977-2 on the ACh-gated Cl- channel conductance or mean open time were observed. The finding that responses to the hydrolysis-resistant cholinergic analogue carbachol were unaffected by the two xanthines suggested that the observed effects were at least partly caused by an inhibition of acetylcholinesterase (AChE) activity. That these substances inhibit AChE activity was confirmed in vitro. Phosphorylation processes nonetheless appear to be partly involved in the synaptic effect of the xanthines as the kinase blocker H-8 blocked part of the IPSC Tc lengthening. Possible mechanisms are discussed.
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PMID:Xanthine derivatives IBMX and S-9977-2 potentiate transmission at an Aplysia central cholinergic synapse. 138 Aug 83

Retinoic acid (RA) induced neuronal differentiation in A126-1B2 cells and 123.7 cells, two mutant lines of PC12 that are deficient in cAMP-dependent protein kinase, but not in the parental PC12 cell line. A single exposure to RA was sufficient to cause neurite formation and inhibit cell division for a period of greater than 3 wk, suggesting that RA may cause a long-term, stable change in the state of these cells. In A126-1B2 cells, RA also induced the expression of other markers of differentiation including acetylcholinesterase and the mRNAs for neurofilament (NF-M) and GAP-43 as effectively as nerve growth factor (NGF). Neither NGF nor RA stimulated an increase in the expression of smg-25A in A126-1B2 cells, suggesting that the cAMP-dependent protein kinases may be required for an increase in the expression of this marker. RA also caused a rapid increase in the expression of the early response gene, c-fos, but did not effect the expression of egr-1. RA equivalently inhibited the division of A126-1B2 cells, 123.7 cells and parental PC12 cells, so RA induced differentiation is not an indirect response to growth arrest. In contrast, the levels of retinoic acid receptors (RAR alpha and RAR beta), and retinoic acid binding protein (CRABP) mRNA were strikingly higher in both A126-1B2 cells and 123.7 cells than in the parental PC12 cells. The deficiencies in cAMP-dependent protein kinase may increase the expression of CRABP and the RARs; and, thus, cAMP may indirectly regulate the ability of RA to control neurite formation and neural differentiation. Thus, RA appears to regulate division and differentiation of PC12 cells by a biochemical mechanism that is quite distinct from those used by peptide growth factors.
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PMID:Retinoic acid stimulates the differentiation of PC12 cells that are deficient in cAMP-dependent protein kinase. 164 38

In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.
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PMID:Research on the differentiation of human and murine neuroblastoma cells. 167 82

1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H7), a potent inhibitor of protein kinase C, induced neuritogenesis in Neuro-2a cells, whereas N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), which inhibits more efficiently cAMP- and cGMP-dependent protein kinases, did not. The effect, noticeable after 3 hr, was maximum (13-fold increase at 500 microM H7) between 1 and 3 days and was maintained over 2 months. In controls, 90% of the cells were undifferentiated, whereas after 3 hr with 500 microM H7 only 25% of the cells remained undifferentiated. DNA synthesis decreased as the number of differentiated cells increased. Differentiation is also functional since acetylcholinesterase activity increased approximately 7-fold after 48 hr with 500 microM H7. Phorbol 12-myristate 13-acetate, a specific activator of protein kinase C, prevented or reversed the induction of neuritogenesis and the inhibition of DNA synthesis by H7. There is a good correlation between the level of protein kinase C and the percentage of differentiated cells. The results indicate that protein kinase C may play a key role in the control of differentiation of neural cells. Some possible clinical implications are briefly discussed.
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PMID:Inhibition of protein kinase C induces differentiation in Neuro-2a cells. 169 37


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