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)

The effects of acetylcholine (ACh) on the depolarization-evoked release of endogenous glutamic acid (Glu) have been studied using synaptosomes prepared from rat hippocampus and depolarized in superfusion with 15 mM KCl. Acetylcholine inhibited Glu release in a concentration-dependent way. The natural agonist was particularly effective causing 50% inhibition of Glu release at 10 microM in the absence of acetylcholinesterase (AChE) inhibitors. The inhibitory effect of ACh on the K+-evoked release of Glu was antagonized by the selective muscarinic receptor antagonist atropine but not by the nicotinic receptor antagonist mecamylamine. The data represent the first demonstration that muscarinic receptors located on Glu axon terminals in rat hippocampus may modulate the release of Glu.
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PMID:Muscarinic inhibition of endogenous glutamate release from rat hippocampus synaptosomes. 256 54

We investigated the erectile response to intracavernous injection of increasing doses of acetylcholine (0.5 to 500 micrograms.) in 10 monkeys. To differentiate between nicotinic (ganglionic) and muscarinic (parasympathetic postganglionic) effects, acetylcholine was likewise administered after 1.6 mg. trimethaphan camsylate and 0.1 mg. atropine, alone or sequentially. Erections were induced by cavernous nerve stimulation before and after atropine. Acetylcholine induced a dose-dependent, triphasic erectile response: a first tumescence phase followed by contraction and a subsequent second phase of tumescence. Atropine reduced but did not abolish the erectile response to acetylcholine: attainment of maximal intracavernous pressure after neurostimulation was both delayed and reduced (mean 25 cm. H2O). Only after combined nicotinic and muscarinic blockade was the erectile response to acetylcholine completely abolished. Histologic staining for acetylcholinesterase in five additional monkeys that had not received acetylcholine showed dense staining within the cavernous erectile tissue and around the cavernous arteries. Our data suggest that acetylcholine is a possible neurotransmitter for penile erection in monkeys.
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PMID:Acetylcholine as a possible neurotransmitter in penile erection. 256 91

In order to obtain further evidence of putative neurotransmitters in primary sensory neurons and interneurons in the dorsal spinal cord, we have studied the effects of unilateral section of dorsal roots and unilateral occlusion of the dorsal spinal artery on cholinergic enzyme activity and on selected amino acid levels in the spinal cord. One week after sectioning dorsal roots from caudal cervical (C7) to cranial thoracic (T2) levels, the specific activity of choline acetyltransferase (ChAT) was significantly decreased and acetylcholinesterase (AChE) showed a tendency to decrease in the dorsal quadrant on the operated side of the spinal cord. Dorsal root sectioning had little effect on the levels of free glutamic acid or other amino acids in the dorsal spinal cord. These results suggest that primary sensory neurons may include some cholinergic axons, and that levels of putative amino acid transmitters are not regulated by materials supplied by axonal transport from the dorsal root ganglia. By contrast, one week following unilateral occlusion of the dorsal spinal artery, the activities of ChAT and AChE were unchanged in the operated quadrant of the spinal cord, while decreases of Asp, Glu, and GABA, and an increase in Tau were detected. These findings are consistent with the proposals that such amino acids, but not ACh, may function as neurotransmitter candidates in interneurons of the dorsal spinal cord.
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PMID:Effects of dorsal root section and occlusion of dorsal spinal artery on the neurotransmitter candidates in rat spinal cord. 256 90

The bronchial smooth muscle of the rat was examined for contractile responses to excitatory amino acids. The nerve-mediated contraction induced by electrical field stimulation was enhanced by exogenous L-glutamate (L-Glu). The apparent affinity (ED50) of L-Glu was 3.5 +/- 0.1 mM. Both tetrodotoxin and hemicholinium-3 completely abolished the electrical field-induced contraction and therefore the potentiation by L-Glu, which indicates that L-Glu has a prejunctional effect. Concentrations of L-Glu higher than 22 mM inhibited the electrical field-induced contractions and enhanced the tonus of the smooth muscle by postjunctional stimulation. The ED50 of exogenous ACh was not altered by L-Glu. High concentrations (62 mM) of L-Glu increased the intrinsic activity (alpha) of ACh, indicating a postjunctional potentiation of ACh-induced contractions. L-Glu did not inhibit the activity of acetylcholinesterase, therefore the postjunctional potentiation was not due to ACh accumulation. Inhibition of the electrical field-induced contraction was seen with high concentrations of D-Glu, L-aspartate (L-Asp), L-alpha-amino adipate and ibotenate. Neither glutamate diethyl ester nor 2-amino-5-phosphonovalerate had any inhibitory effects on the L-Glu- and L-Asp-induced alterations of the electrical field-stimulated contraction or on the L-Glu-enhanced tonus of the bronchial smooth muscle. Kainate, N-methyl-D-aspartate, quisqualate and N-acetyl-aspartyl-glutamate had only minor transient potentiating effects on the electrical field-induced contraction. The results provide evidence for a L-Glu receptor in rat bronchi that has a different specificity for glutamate agonists and antagonists than the L-Glu receptor described in the CNS. The receptor seems to be located prejunctionally and enhances nerve-mediated responses and thereby stimulates the bronchial smooth muscle to contract. The possible involvement of this type of receptor in the 'Chinese restaurant syndrome' is discussed.
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PMID:Stimulation of peripheral cholinergic nerves by glutamate indicates a new peripheral glutamate receptor. 256 40

Famotidine and selected H2-antagonists were evaluated with respect to toxicity and selected pharmacological activities. When administered intraperitoneally to mice at a dose equivalent to 10 times their respective H2-antagonist ED50 values, no deaths were observed. Similarly, no alteration in brain ACh concentrations or overt pharmacological effects were noted. However, at 400 mg/kg, ranitidine produced 89% lethality, followed by cimetidine (11%) and famotidine. Only cimetidine and famotidine at this dose significantly elevated brain acetylcholine levels. These results do not correlate with the in vitro data, where ORF-17578 and ranitidine were the most potent entities with respect to acetylcholinesterase inhibition (approximately 1-2 X 10(-6) M), followed by nizatidine greater than cimetidine greater than famotidine. The sulfoxide metabolites of ranitidine and cimetidine were approximately one-tenth as potent as their parent compounds with respect to inhibition of acetylcholinesterase. Direct muscarinic stimulation or potentiation of acetylcholine-induced contraction in ileal tissue was not observed for any of the H2-antagonists.
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PMID:A comparison of the cholinergic activity of selected H2-antagonists and sulfoxide metabolites. 257 49

The concentration-dependent actions of neostigmine, a carbamate anticholinesterase agent, were studied on the acetylcholine receptor channel complex in voltage-clamped twitch fibers of costocutaneous muscles of garter snakes. Low concentrations of neostigmine (10(-6) or 10(-5) M) increased miniature endplate current (MEPC) amplitude and the time constant of MEPC decay without changing the relationship between the MEPC decay time constant and membrane potential. Acetylcholine- or carbachol-induced endplate current fluctuation spectra were well fitted by a single Lorentzian curve with a characteristic frequency and single-channel conductance unaltered by low concentrations of neostigmine. Concentrations of neostigmine greater than 5 X 10(-5) M decreased MEPC amplitude and split the decay of MEPCs into two components, one faster and one slower than the control rate. These effects were both voltage and concentration dependent. Spectra of current fluctuations recorded in concentrations greater than or equal to 5 X 10(-5) M neostigmine required two time constants, one faster and one slower than the control. Two component spectra were also obtained with carbachol-induced current fluctuation spectra, indicating that these effects of neostigmine were direct and not a consequence of acetylcholinesterase inhibition. Similar results were also obtained in muscles pretreated with collagenase to remove junctional acetylcholinesterase. The fast and slow time constants obtained from current fluctuation spectra decreased and increased, respectively, with either increases in the concentration of neostigmine or membrane hyperpolarization when analyzed in the same fiber. The effects of neostigmine on channel lifetime were reversible with washing. These results indicate that the effects of neostigmine are concentration dependent. Concentrations greater than 2.5 X 10(-5) M exhibit direct effects on the endplate receptor channel complex which are unrelated to acetylcholinesterase inhibition. These actions include: a prolongation of the gating kinetics of the endplate receptor channel complex, the production of an altered state of the receptor channel complex evidenced by a high frequency component to current fluctuation spectra, and a direct action to block the acetylcholine receptor.
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PMID:Concentration-dependent effects of neostigmine on the endplate acetylcholine receptor channel complex. 257 18

Acetylcholine increased twitch tension in the whole ventricle or in ventricular strips from 2-10-day chick embryos. The effect of acetylcholine was mediated by muscarinic receptors, since it was prevented by atropine, but not by tubocurarine or propranolol. Prostigmine significantly increased the sensitivity to acetylcholine in the strips from 7-day embryos, being almost ineffective in the strips from 3-day embryos. The decrease in acetylcholine sensitivity in the developing chick embryo is presumably associated with the increase in cholinesterase activity of the myocardial tissue.
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PMID:[Positive inotropic action of acetylcholine on the heart ventricles of the chick embryo]. 259 11

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49

Since the function of the brain is considered to be a sum of synaptic transmission phenomena, information on both neurotransmitters and receptors are needed. In addition, experiments of behavioral pharmacology to determine whether the neuron network is in operation or not are indispensable. Acetylcholine (ACh) is difficult to measure in the postmortem brain because of rapid postmortem degradation, and thus the activity of choline acetyltransferase (CAT), a synthetic enzyme, is determined. Receptors for ACh system are classified into muscarinic ACh receptors (MCR) and nicotinic ACh receptors (NCR). Since ACh and MCR/NCR are contained in different neurons, their regional distributions mismatch. Therefore, to evaluate the relationship between the ACh neuronal system and aging or dementia, information on all steps of CAT, receptors, memory and learning experiments are needed. Both in the normally aged brain and ATD brain, the ACh neuronal system at all steps is decreased except an increase in ACh degradation enzyme (acetylcholinesterase) in the normally aged brain. In animals, the decreased ACh neural system associated with aging can be normalized by drugs, showing that the aged brain still has plasticity. On the other hand, autoradiography of MCR in the ATD brain demonstrated destruction of the laminar structure of the cerebral cortex. This suggests that drugs to increase only ACh are not effective for treating ATD. In ATD, treatment methods that prevents structural destruction or its progression should be developed.
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PMID:[Central acetylcholinergic systems in the normal aged and in the patient with Alzheimer-type dementia (ATD)]. 269 98

Although acetylcholine is known to be involved in the genesis of skeletal muscle disturbance, its effect on cardiac muscle has been scarcely studied. In the present paper, using pyridostigmine, a cholinesterase inhibitor, the possible role of acetylcholine in the genesis of cardiomyopathy was investigated. In a mortality study, it was shown that pyridostigmine (100 mg/kg) caused death of 9/10 rats within 8 h, and that the lethality of such a dose could be significantly diminished by the subsequent administration of a total dose of 4 mg/kg atropine. In all other experiments, rats were divided into three groups; the control, untreated group; the pyridostigmine + atropine group in which atropine (2 mg/kg) was administered 5 min after pyridostigmine (60 mg/kg) administration; and the pyridostigmine group in which pyridostigmine (60 mg/kg) was administered orally. Rats were killed 3 h after pyridostigmine administration, and hearts were isolated. Heart mitochondrial electron transport activity (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) were measured enzymatically, and mitochondrial respiratory rates and control indices were measured polarographically. Structural changes in cardiac muscles of each group were observed by electron microscopy of cardiac sections. Acetylcholine levels of left ventricle were measured by high performance liquid chromatography. Activities of NADH-cytochrome c reductase and succinate-cytochrome c reductase were not affected by pyridostigmine administration; however, cytochrome c oxidase activity was significantly reduced in the pyridostigmine group. Atropine markedly lessened this reduction in activity. A protective effect of atropine was also observed morphologically. A protective effect of atropine was also observed morphologically. In the pyridostigmine group and the pyridostigmine + atropine group, left ventricular acetylcholine levels were increased significantly compared with the control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of acetylcholine in pyridostigmine-induced myocardial injury: possible involvement of parasympathetic nervous system in the genesis of cardiomyopathy. 273 Mar 38


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