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

We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from 21 2-wk-old swine (2ws) and 19 10-wk-old swine (10ws) were tethered isometrically at optimal resting length, and responses were expressed as percent of the maximum to 63 mM potassium-chloride (%KCl). Cumulative concentration-response curves to KCl were equivalent for TSM from 2 and 10ws. However, maximal contraction to ACh in 2ws (168 +/- 8.4 %KCl) was greater than for 10ws (142 +/- 2.3 %KCl; P less than 0.02). Stimulus-response curves (field electrodes; AC source) demonstrated greater sensitivity for TSM in 10ws (stimulus causing 50% of the maximal response = 3.32 +/- 0.13 V in 2ws vs. 2.25 +/- 0.12 V in 10ws; P less than 0.001), indicating that the greater cholinomimetic responsiveness of 2ws did not result from augmented presynaptic nerve conduction. The AChase inhibitor, physostigmine, caused 1) greater sensitivity of responses elicited by electrical field stimulation in 2ws (P less than 0.05) but not in 10ws (P = NS), 2) augmentation of maximal responses to exogenous ACh in 10ws (27% increase; P less than 0.01) but not 2ws (2% increase; P = NS), and 3) a greater increase in sensitivity to cholinomimetic activation in 2ws compared with 10ws (P less than 0.02). These data demonstrate increased cholinergic contraction of TSM in 2 vs. 10ws that results at least in part from reduced AChase activity in the trachea of immature animals.
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PMID:Maturation of acetylcholinesterase expression in tracheal smooth muscle contraction. 238 31

The actions of two reversible anticholinesterase agents, edrophonium and physostigmine, were compared with the irreversible agent methanesulfonyl fluoride (MSF) on miniature end-plate currents (MEPCs) and ACh-induced end-plate current fluctuations recorded from twitch fibers of costocutaneous muscles of garter snakes (Thamnophis sp.). Low concentrations of edrophonium (less than 25 microM) produced a concentration-dependent increase in both the MEPC amplitude and the time constant of MEPC decay. MEPCs recorded at all concentrations studied (25-100 microM) decayed as a single exponential function with time. As the concentration of edrophonium was increased, MEPC amplitude was initially increased and then decreased such that, at concentrations above 50 microM, MEPC amplitude was decreased below control values. Concentrations of edrophonium greater than 30 microM produced power density spectra that required the sum of two Lorentzian components--one faster and one slower than control. Single-channel conductance was not significantly altered by edrophonium. Low concentrations of physostigmine (less than 10 microM) increased MEPC amplitude and prolonged MEPC decay. Higher concentrations of physostigmine (10-100 microM) decreased mean peak MEPC amplitude and accelerated MEPC decay in a concentration-dependent manner. The relationship between MEPC decay and membrane potential was reduced, and then reversed, with increasing concentrations of physostigmine. Current fluctuation spectra recorded in physostigmine were described by a single Lorentzian function at all membrane voltages and concentrations studied. Increasing the concentration of physostigmine or membrane hyperpolarization did not alter single-channel conductance but shortened the apparent lifetime of open end-plate channels. MSF increased MEPC amplitude and increased the time constant of MEPC decay without altering the temperature and voltage dependence of both MEPC decay and channel lifetime determined from end-plate current fluctuations. Exposure of MSF-treated end-plates to either edrophonium or physostigmine produced results that were similar to those obtained before MSF treatment. These results demonstrate that edrophonium and physostigmine have direct actions on the end-plate receptor-channel complex that are unrelated to their inhibitory action on junctional acetylcholinesterase.
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PMID:Interactions of edrophonium, physostigmine and methanesulfonyl fluoride with the snake end-plate acetylcholine receptor-channel complex. 241 11

In rats the effect of inhibition of the brain cholinesterase activity on the pressor and heart rate responses to 5-hydroxytryptamine (5-HT), administered into the lateral cerebral ventricle (l.c.v.) was examined. After administration of physostigmine (twice in a small dose of 2.5 micrograms l.c.v., 20 and 15 min before the second injection of 5-HT), the pressor effect of 5-HT (5 micrograms) was strongly reduced or almost abolished, its pure tachycardia was reduced or reversed into a bradycardia and its pure bradycardia was diminished or reversed into a tachycardia. The type of the cardiovascular response to ACh (5 micrograms l.c.v., 20 min after the second administration of 5-HT) indicates that the modification of the cardiovascular response to 5-HT was accompanied by inhibition of the brain cholinesterase activity. Thus, it seems that a functionally competent cholinesterase in the brain is necessary for the generation of the 5-HT-induced pressor response. The present experiments provide further evidence that there is a cholinergic link in the pathway by which serotonergic mechanisms in the preoptic-anterior hypothalamic area rise blood pressure and support the idea that the same link exists in the pathway(s) mediating the heart rate responses to intracerebroventricular administration of 5-HT.
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PMID:Modification by physostigmine of the cardiovascular responses to intracerebroventricular administration of 5-hydroxytryptamine in rats. 244 83

The properties of acetylcholine receptor (AChR) channels on chick ciliary ganglion neurons in culture were examined using patch-clamp recording techniques. Acetylcholine (ACh) was applied by rapid microperfusion. Whole-cell current noise analysis revealed a single class of functional receptors on the neurons. Dose-response studies indicated a Kd of about 36 microM and a Hill coefficient of 1.5-1.7, predicting 2 ACh binding sites per receptor. Both fast and slow components of receptor desensitization were observed. Single-channel recordings from excised outside-out patches of soma membrane exposed to 2-5 microM ACh indicated a single-channel conductance of 40 pS, a reversal potential of -9 mV, a mean open duration of 1 msec, and an opening probability of 0.34. The kinetic behavior of the channels was provisionally described by a 3-closed, 1-open state model for receptor activation. In all of these properties, AChRs of ciliary ganglion neurons resemble those on skeletal muscle fibers. Growing the neurons in an elevated K+ concentration produced a 2-3-fold decrease in peak whole-cell currents induced by ACh under standard test conditions, without altering any of the single-channel properties described above. Neither changes in cholinesterase activity nor receptor distribution accounted for the decrease. Instead, calculations indicated that elevated K+ reduced the ACh response by decreasing the number of functional AChRs on the neurons. No K+-dependent decrease is observed, however, in the number of total receptors on the neurons detected either by a monoclonal antibody specific for the receptor or by an alpha-neurotoxin that binds to the receptor and blocks its function. Moreover, the number of receptors detected by the 2 probes is at least 10-fold greater than the calculated number of functional receptors. The findings suggest that only a small fraction of the AChRs on the neuronal surface is functional and that the cell can alter the ratio of functional and nonfunctional receptors in response to growth conditions.
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PMID:The properties and regulation of functional acetylcholine receptors on chick ciliary ganglion neurons. 244 40

Acetylcholine (ACh)-activated channels in end-plates of frog sartorius muscle were studied at various times after denervation. Mean open times of the synaptic membrane channels were derived from the time constant of decay of miniature end-plate currents (tau MEPC) evoked by ACh quanta released from Schwann cells, which replace the motor nerve terminals after these degenerate. Membrane current noise, elicited by iontophoretic application of ACh to voltage-clamped end-plates, was also used to determine mean open time (tau noise) and conductance of the ion channels. About 1 week after denervation, soon after Schwann cell MEPCs appeared, they had a tau similar to that of the neural MEPC in innervated end-plates. However, 5-6 weeks after denervation tau MEPC was increased by a factor of about 5. Circa 4 weeks after denervation, cholinesterase activity of the denervated muscle decreased to 76% of that in the contralateral, innervated muscle, and even 4 months after the operation it was still 64%. Thus, it is unlikely that a change in acetylcholinesterase activity is the main factor responsible for the increase in tau of Schwann cell MEPC. About 1 week after denervation tau noise was close to that in innervated end-plates (about 2 ms). Twelve to 24 days after denervation the average channel open time was 4.5 +/- 1.0 ms, with some end-plates still showing normal 'fast' channels. However, in muscles denervated for 47-113 days the open time was 12.9 +/- 1.9 ms. In the early and intermediate periods, ACh-induced noise spectra with two components were obtained from many end-plates, indicating the simultaneous activation of two different types of channels. At some end-plates during the early and intermediate periods after denervation, but not after about 5 weeks, neostigmine caused the appearance of a component, which was as fast as that of normal end-plate channels. In other experiments small doses of alpha-bungarotoxin were applied in order to predominantly block extra-junctional receptors. In the early period of denervation, when two components were present in the noise spectra, alpha-bungarotoxin eliminated the slow component leaving channels as fast as in innervated end-plates. After prolonged denervation, a component with tau of about 5.5 ms was occasionally disclosed by application of alpha-bungarotoxin. tau noise and tau MEPC from the same end-plate closely agreed. Our results indicate that at frog end-plates the open time of the majority of the synaptic channels opened by ACh becomes longer with increasing time after denervation.
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PMID:Changes in the properties of synaptic channels opened by acetylcholine in denervated frog muscle. 246 37

Acetylcholine, substance P and nitroglycerin applied intra- and extraluminally to the perfused dog femoral artery segment with endothelium caused depressor responses. Endothelium denudation abolished the responses to acetylcholine and substance P. EC50 ratios of extra- versus intraluminal acetylcholine and substance P were 43 and 79, respectively, whereas those of nitroglycerin did not differ. Physostigmine potentiated the response to extraluminal acetylcholine. Acetylcholine seems to be degraded partly by cholinesterase in the arterial wall. Acetylcholine and substance P applied extraluminally are expected to reach the endothelium and release endothelium-derived relaxing factor.
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PMID:Extraluminally applied acetylcholine and substance P on the release of EDRF. 247 88

Incubation of cultured rat pituitary cell aggregates with [3H]choline ([3H]Chol) yielded a derivative that was identified as [3H]acetylcholine ([3H]ACh) by several criteria: 1) the [3H]Chol derivative with the highest retention time coeluted with a [14C]ACh standard in cation exchange and reverse phase HPLC; 2) cholinesterase treatment converted this derivative to a substance with the retention time of [3H]Chol; 3) two blockers of ACh production, hemicholinium and 4-[(1-naphthylvinyl)pyridinium], eliminated 3H-labeled material in the HPLC fractions with ACh retention time. Spontaneous [3H]ACh release was increased by depolarizing potassium concentrations, and both synthesis and release of ACh were increased by the glucocorticoid hormone dexamethasone. Double immunostaining of choline acetyltransferase (CAT) and, respectively, of ACTH, GH, PRL, TSH, S100, LH, and FSH in rat pituitary cells revealed that most of the CAT-immunoreactive cells were also ACTH immunoreactive. A small proportion (less than 10%) of the PRL-immunoreactive cells also showed CAT immunoreactivity, but all other cell types were negative. The immunocytochemical evidence for colocalization of CAT within the ACTH cell was strengthened by the finding of a significantly higher rate of [3H]ACh synthesis in a corticotroph-enriched cell population obtained by separating pituitary cells on a velocity sedimentation gradient. In addition, the mouse pituitary corticotropic cell line AtT20 contained CAT immunoreactivity, converted [3H]Chol to [3H]ACh, and released bioactive ACh-like material. In conclusion, the present data provide strong evidence that pituitary corticotrophs synthesize and release ACh, and that the activity of this intrapituitary cholinergic transmission system is under regulatory control.
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PMID:Synthesis and release of acetylcholine by normal and tumoral pituitary corticotrophs. 253 72

We examined neurochemically the effects of bifemelane (BF) on muscarinic ACh (mACh-R) and beta-adrenergic receptors (beta-AdR) and imipramine binding sites and the activities of acetylcholinesterase (AChE), choline acetyltransferase (CAT) and monoamine oxidase (MAO) in the P2 fractions of rat brain, ex vivo and in vitro. Male rats were given daily injections of 10, 30 mg/kg BF, p.o., for a period of 4 weeks. The Kd and Bmax values for mACh-R in the rat forebrain by administration of 10, 30 mg/kg BF decreased significantly compared with that of the control, although the Kd and Bmax values for beta-AdR and imipramine binding sites were almost identical. The Km and Vmax values of A- and B-form MAO decreased in rats that had been administered 30 mg/kg BF for 4 weeks. The binding of 3H-QNB (quinuclidinyl benzilate) on mACh-R, 125I-CYP (iodocyanopindolol) on beta-AdR and 3H-imipramine on imipramine binding sites decreased by 60, 20 and 70% in the presence of 1 microM BF, respectively, while the addition of 1 microM BF inhibited MAO activity by about 50%. However, CAT and AChE activities were not inhibited by BF.
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PMID:[Neurochemical studies on bifemelane, a new cerebral function improver. I. Effects of bifemelane on the function of neurotransmission-related enzymes and receptors in rat brain]. 254 82

Chick ciliary ganglion neurons have nicotinic acetylcholine receptors (AChRs) that mediate chemical transmission through the ganglion, and GABAA receptors of unknown significance. Previous experiments examining the role of cell-cell interactions in regulating neuronal AChRs have shown that postganglionic axotomy of ciliary ganglia in newly hatched chicks causes a 10-fold decline in total AChRs within 5 d compared with unoperated contralateral ganglia and that preganglionic denervation causes a 3-fold decline within 10 d. Many of the AChRs are known to be intracellular; of those present on the cell surface, only a small fraction appears to be functionally available normally. In the present experiments, the effects of the operations on functional AChRs and GABAA receptors in the plasma membrane of the neurons were examined by removing the ganglia 5 d after axotomy or 10 d after denervation, dissociating them into single cells, and immediately measuring their ACh and GABA sensitivities with intracellular recording techniques. The ACh sensitivity of axotomized ciliary ganglion neurons was reduced 10-fold compared with neurons from unoperated contralateral ganglia of the same chicks. The reduction could be largely accounted for by a decrease in the maximum response and did not arise from a change either in the dose-response curve or the acetylcholinesterase activity of the neurons. Autoradiographic studies using a radiolabeled anti-AChR monoclonal antibody also demonstrated a substantial decrease in the total number of surface AChRs associated with axotomized neurons. In contrast, axotomy had no unilateral effect on the GABA response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of nerve transection on the ACh and GABA receptors of chick ciliary ganglion neurons. 255 59

1. Desensitization of the nicotinic acetylcholine receptor of the frog end-plate was investigated in dissociated frog muscle fibres using the Vaseline-gap clamp method so that a wide range of well-defined agonist concentrations could be used without having to use alpha-bungarotoxin to reduce currents, and so that the intracellular medium could be controlled. 2. Acetylcholine (ACh) concentrations between 1 and 1000 microM were used, after inactivation of acetylcholinesterase. The intracellular calcium concentration was usually kept near zero by using 80 mM-K2EGTA as the intracellular solution. 3. When using the low intracellular calcium solution, desensitization proceeded as a biphasic process with estimates of fast and slow time constants of about 8 and 80 s at 4 degrees C and 20 microM-ACh (the rates increased with concentration). In contrast, only one (fast) component of desensitization was detected when the intracellular calcium concentration was allowed to increase during ACh application. 4. Despite rapid application of ACh the time to peak response was 0.2 s (with 400 microM-ACh) to 2 s (with 1 microM-ACh); this slow rise was shown to result from diffusion delays. Nevertheless the peak current with 200 microM-ACh corresponded to opening of most of the channels present, so there is probably not much desensitization in the millisecond time range. 5. Both fast and slow time constants for onset of desensitization showed only slight dependence on membrane potential when [Ca2+]i was buffered with 80 mM-K2EGTA. 6. Increasing the intracellular cyclic AMP concentration directly, or indirectly with forskolin and IBMX, had no effect on the time course of desensitization. 7. Intracellular application of submicromolar concentrations of phorbol-12,13-dibutyrate (PDBu) and phorbol-12-myristate-13-acetate (PMA) yielded a small but reproducible reduction of the peak response to ACh. The time course of desensitization was, however, not modified by these substances. 8. The implications of these observations for the mechanism of desensitization, and their relationship to single-channel observations, are discussed.
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PMID:Desensitization of the acetylcholine receptor of frog end-plates measured in a Vaseline-gap voltage clamp. 256 85


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