Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 A number of criteria for considering adenosine 5'-triphosphate (ATP) as a neurotransmitter in the guinea-pig urinary bladder have been examined. In addition, the effect of tachyphylaxis to ATP on the response to non-adrenergic, non-cholinergic nerve stimulation has been re-examined.2 Quinacrine fluorescence histochemistry revealed a population of nerve fibres, ganglion cells, and nerve bundles in the bladder which were not seen in either the iris or vas deferens, where adrenergic and cholinergic nerves predominate. The distribution and morphology of the quinacrine-positive nerves in the bladder were different from those observed with catecholamine fluorescence and cholinesterase histochemistry, and were unaffected by chemical sympathectomy.3 Release of ATP from the bladder during stimulation of intramural excitatory nerves, in the presence of atropine and guanethidine increased to 3-12 times prestimulation levels. Tetrodotoxin abolished both the contractile response and the increase in ATP release resulting from intramural nerve stimulation. There was no increase in ATP release during contraction resulting from direct muscle stimulation following nerve paralysis with tetrodotoxin.4 Sympathectomy with 6-hydroxydopamine did not affect release of ATP in response to intramural nerve stimulation.5 Release of ATP was dependent on the concentration of calcium ion in the medium.6 Contractions in response to non-adrenergic, non-cholinergic intramural nerve stimulation were closely mimicked by ATP, but not by acetylcholine or histamine.7 Adenosine and dipyridamole reduced the contractions to both ATP and non-cholinergic nerve stimulation.8 2-2'-Pyridylisatogen was not a specific blocker of either ATP or intramural nerve stimulation in the guinea-pig bladder. 2-Substituted imidazolines initiated spontaneous activity making it impossible to assess any blocking action that they may have had.9 Prostaglandins (E(1), E(2) and F(2alpha)) gave weak, slow contractions and an increase in spontaneous activity. Both the response to ATP and non-adrenergic, non-cholinergic nerve stimulation were greatly potentiated in the presence of prostaglandins.10 In the presence of indomethacin the response to non-adrenergic, non-cholinergic nerve stimulation was virtually abolished following desensitization to ATP.
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PMID:Purinergic innervation of the guinea-pig urinary bladder. 2 86

The interaction between bombesin and acetylcholine acting on smooth muscle of the stomach wall was investigated in two species of teleost fish. Oncorhynchus mykiss (rainbow trout) and Gadus morhua (Atlantic cod). Acetylcholine or bombesin alone has an excitatory effect on the stomach muscle. The effect on contraction amplitude of acetylcholine (10(-6)-10(-5) M) alone is about 10-times greater than the effect of bombesin (10(-9)-10(-7) M). In molar terms however, bombesin is more potent than acetylcholine. Bombesin (10(-8)-10(-7) M) added 0.5-3 min prior to acetylcholine potentiates the effect of acetylcholine in a dose-dependent manner. The potentiation is most pronounced in circular muscle preparations, but is present also in longitudinal muscle preparations. Bombesin affects the response to carbachol (10(-6) M) with a similar potentiation, indicating that the potentiation is not caused by inhibition of choline esterase activity. Atropine (10(-6)-10(-5) M) abolishes the response to bombesin plus acetylcholine as well as the response to acetylcholine alone. Tetrodotoxin (10(-6) M) does not block the effect of acetylcholine, bombesin or the combination acetylcholine plus bombesin. Substance P (10(-9)-10(-7) M) which has a similar excitatory effect on the stomach muscle as bombesin, does not potentiate the effect of acetylcholine. Immunohistochemistry has shown the presence of strong bombesin-like immunoreactivity in stomach nerves of the cod and weak bombesin-like immunoreactivity in rainbow trout nerves. In addition, bombesin-like immunoreactivity was demonstrated in endocrine cells in the gastric and intestinal mucosa of both species. It is concluded that bombesin, contained either in nerve fibres or in mucosal endocrine cells, specifically potentiates the effect of acetylcholine in the fish stomach.
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PMID:Bombesin potentiates the effect of acetylcholine on isolated strips of fish stomach. 170 14

A vertical-type in vivo microdialysis probe and a sensitive, specific radioimmunoassay (RIA) were used to study the mechanism of acetylcholine (ACh) release in the striatum of anesthetized rats. Without the use of physostigmine, a cholinesterase inhibitor, our RIA could still detect the amount of ACh present in the perfusate (5.6 +/- 0.6 fmol/min, n = 16). Tetrodotoxin (1 microM) produced a significant decrease in the amount of ACh collected in the perfusate, suggesting that basal ACh determined under the present experimental conditions was related to cholinergic neural activity. Atropine (0.1-1 microM) applied topically via the dialysis probe did not affect the amount of ACh recovered in the perfusate in the absence of physostigmine. Addition of physostigmine (10 microM) to the perfusion fluid produced about a 100-fold increase in the amount of ACh collected. In the presence of physostigmine, topical administration of atropine and pirenzepine (0.01-1 microM) through a dialysis probe produced a further three- to fourfold increase in ACh output, whereas a slight increase was produced by AF-DX 116 at the highest concentration (1 microM). These results indicate that presynaptic modulation of ACh release in the striatum does not occur under basal conditions, and that presynaptic M1 muscarinic receptors are involved in the modulation of ACh release when the ACh concentration is raised under certain conditions.
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PMID:Determination of acetylcholine release in the striatum of anesthetized rats using in vivo microdialysis and a radioimmunoassay. 186 Nov 56

A radioisotope method has been developed for measuring the stimulation-evoked release of acetylcholine without the use of cholinesterase inhibitors from the mouse hemidiaphragm preparation which had been loaded with 3H-choline. Evidence has been obtained that 3H-choline was taken up by and released from both innervated and non-innervated mouse hemidiaphragm preparations. However, it was released in the form of 3H-acetylcholine in response to electrical field stimulation only from the innervated preparations. Long lasting (51 min) S1 stimulation of the preparations exhausted the radioactive acetylcholine stores to the extent that S2 did not evoke any release of 3H. These data suggest that when the labelled acetylcholine stores become exhausted, the labelled choline, still present in the tissue, cannot be released by electrical stimulation. Tetrodotoxin (1 mumol/l) administration and Ca withdrawal inhibited, 20-100 mumol/l 4-aminopyridine enhanced the release of 3H-acetylcholine in response to electrical stimulation. Activation of the presynaptic muscarinic receptors by the agonist oxotremorine (50 mumol/l) decreased the liberation of 3H-acetylcholine. The muscarinic antagonist atropine (1 mumol/l) abolished the inhibitory effect of oxotremorine and by itself increased the evoked release of the newly formed 3H-acetylcholine. Adenosine (50 mumol/l) reduced the evoked release of radioactivity. Theophylline (30 mumol/l) prevented the inhibitory effect of adenosine and itself enhanced the release. Xylazine (1 mumol/l), an alpha 2-adrenoceptor agonist did not affect the release. It is concluded that the stimulation-evoked release of 3H-acetylcholine from the mouse phrenic nerve hemidiaphragm preparation preloaded with 3H-choline is derived from the motor nerves. The release of acetylcholine is modulated by activation of presynaptic muscarinic and adenosine receptors.
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PMID:Modulation of stimulation-evoked release of newly formed acetylcholine from mouse hemidiaphragm preparation. 281 46

1. Studies of the synthesis and release of radioactive acetylcholine in rat brain-cortex slices incubated in Locke-bicarbonate-[U-(14)C]glucose media, containing paraoxon as cholinesterase inhibitor, revealed the following phenomena: (a) dependence of K(+)-or protoveratrine-stimulated acetylcholine synthesis and release on the presence of Na(+) and Ca(2+) in the incubation medium, (b) enhanced release of radioactive acetylcholine by substances that promote depolarization at the nerve cell membrane (e.g. high K(+), ouabain, protoveratrine, sodium l-glutamate, high concentration of acetylcholine), (c) failure of acetylcholine synthesis to keep pace with acetylcholine release under certain conditions (e.g. the presence of ouabain or lack of Na(+)). 2. Stimulation by K(+) of radioactive acetylcholine synthesis was directly proportional to the external concentration of Na(+), but some synthesis and release of radioactive acetylcholine occurred in the absence of Na(+) as well as in the absence of Ca(2+). 3. The Na(+) dependence of K(+)-stimulated acetylcholine synthesis was partly due to suppression of choline transport, as addition of small concentrations of choline partly neutralized the effect of Na(+) lack, and partly due to the suppression of the activity of the Na(+) pump. 4. Protoveratrine caused a greatly increased release of radioactive acetylcholine without stimulating total radioactive acetylcholine synthesis. Protoveratrine was ineffective in the absence of Ca(2+) from the incubation medium. It completely blocked K(+) stimulation of acetylcholine synthesis and release. 5. Tetrodotoxin abolished the effects of protoveratrine on acetylcholine release. It had blocking effects (partial or complete) on the action of high K(+), sodium l-glutamate and lack of Ca(2+) on acetylcholine synthesis and release. 6. Unlabelled exogenous acetylcholine did not diminish the content of labelled tissue acetylcholine, derived from labelled glucose, suggesting that no exchange with vesicular acetylcholine took place. In the presence of 4mm-KCl it caused some increase in the release of labelled acetylcholine. 7. The barbiturates (Amytal, pentothal), whilst having no significant effects on labelled acetylcholine synthesis in unstimulated brain except at high concentration (1mm), diminished or abolished (at 0.25 or 0.5mm) the enhanced release of acetylcholine, due to high K(+) or lack of Ca(2+). The fall in tissue content of acetylcholine, due to lack of Ca(2+), was diminished or abolished by pentothal (0.25 or 0.5mm) or Amytal (0.25mm).
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PMID:Control of synthesis and release of radioactive acetylcholine in brain slices from the rat. Effects of neurotropic drugs. 472 96

1. Cortical slices from rat brain were incubated in media containing the irreversible cholinesterase inhibitor soman and a high KCl concentration, and the release and synthesis of acetylcholine (ACh) were determined.2. Atropine enhanced the release and synthesis of ACh.3. Tetrodotoxin, a substance which blocks nervous conduction, did not influence the release and synthesis of ACh, in the absence or in the presence of atropine. Therefore the nerve endings are probably the site at which atropine acts when stimulating the release and synthesis of ACh.4. Pretreatment of the slices with botulinum type A toxin partially blocked the release and synthesis of ACh and reduced the extra amounts of ACh released and synthesized under the influence of atropine.5. Lowering the calcium or raising the magnesium concentration in the incubation medium reduced the release and synthesis of ACh and their enhancement by atropine.6. Physostigmine decreased the total extractable ACh content of the slices during incubation in a 25 mM KCl containing medium. This decrease was nearly prevented when the release and synthesis of ACh were inhibited by omission of the calcium ions from the medium, but was enhanced by atropine.7. The observations made with pretreatment by botulinum type A toxin, with changes in the calcium and magnesium concentration as well as with physostigmine, all support the theory that it is primarily the release of ACh which is enhanced by atropine and that its stimulating action on the synthesis results from the increased release.
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PMID:Stimulation by atropine of acetylcholine release and synthesis in cortical slices from rat brain. 549 92

The release of vasoactive intestinal peptide (VIP) from the canine gut and its possible neural origin were studied using two agents, oxytocin and neostigmine, known to increase peripheral levels of VIP. Oxytocin and neostigmine increased the portal concentrations of VIP by threefold and sevenfold, respectively. A considerable portal/femoral vein gradient ranging from twofold in the basal state to sevenfold during stimulation with neostigmine indicated that the gut was the main source of circulating VIP. The contribution of the brain was minor, and that of the uterus was undetectable. Release of VIP occurred from the entire gut: After enterectomy, the residual gut (stomach, pancreas, and proximal duodenum) released spontaneously a large amount of VIP which masked the effect of oxytocin. Tetrodotoxin and hexamethonium, but not atropine, inhibited oxytocin-stimulted release of VIP by 80% and 60% respectively. This prompted the conclusion that the release of VIP was predominantly neurally mediated and that the chain of transmission involved a preganglionic cholinergic pathway. Hexamethonium strongly inhibited neostigmine-stimulated release of VIP. Atropine was even more potent in that it abolished the effect of neostigmine. The effect of atropine was attributed to a blockade of ganglionic muscarinic receptors, which are preferentially activated by cholinesterase inhibitors like neostigmine. The results of this study and those derived from electrical stimulation of the vagus nerve are consistent with the hypothesis that circulating VIP is released from intrinsic neurons of the gut under preganglionic cholinergic control.
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PMID:Neural release of vasoactive intestinal peptide from the gut. 743 34

We examined whether cholinesterase inhibitors (ChEI) could alter the release of amyloid precursor protein (APP) from superfused brain cortical slices of the rat. Three ChEI, both reversible and irreversible, were tested for their ability to enhance the release of nonamyloidogenic soluble derivatives (APPs). These included: physostigmine (PHY), heptyl-physostigmine (HEP) and 2,2-dichloro-vinyldimethyl phosphate (DDVP), at concentrations producing cholinesterase (ChE) inhibition ranging from 5% to 95%. All three ChEI elevated APPs release significantly above control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed after muscarinic receptor stimulation with bethanechol (BETHA). Tetrodotoxin (TTX) completely blocked the effect of electrical stimulation. These findings suggest that administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal APP processing.
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PMID:Cholinesterase inhibitors increase secretion of APPs in rat brain cortex. 760 15

Cholinergic modulation of [3H]acetylcholine release evoked by electrical stimulation was studied in the rat major pelvic ganglion, which was prelabeled with [3H]choline. Acetylcholine (ACh) release was independent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 microM) or omission of Ca2+ from the medium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 microM) increased release (by 136%), whereas the M2 muscarinic agonist oxotremorine (1 microM) decreased ACh release (by 22%). The muscarinic antagonists, atropine (1 microM) or pirenzepine (M1 selective, 1 microM), did not change ACh release. However, pirenzepine (1 microM) blocked the facilitatory effect of McN-A 343, and atropine (1 microM) blocked the inhibitory effect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 microM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 microM), and the nicotinic antagonist D-tubocurarine (50 microM) did not change ACh release. 4-Aminopyridine, a K+ channel blocker, significantly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic nerve terminals rather than from the cholinergic cell bodies and is not modulated by actions of endogenous ACh on either muscarinic or nicotinic autoreceptors. These data confirm and extend previous electrophysiological findings indicating that synapses in the major pelvic ganglion have primarily a relay function.
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PMID:Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat. 832 60

In this study we examined the question whether cholinesterase inhibitors (ChEI) could alter the release of amyloid precursor protein (APP) from superfused brain cortical slices of the rat following electrical as well as pharmacological stimulation with bethanechol (BETHA). Three ChEI, both reversible and irreversible were tested for their ability to enhance the release of non-amyloidogenic soluble derivatives (APPs). These included physostigmine (PHY), heptyl-physostigmine (HEP) and 2,2-dichlorovinyldimethyl phosphate (DDVP), at the concentrations producing cholinesterase (ChE) inhibition ranging from 5% to 95%. All three ChEI elevated APPs release significantly above control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed after muscarinic receptor stimulation with BETHA. Tetrodotoxin (TTX) completely blocked the effect of electrical stimulation. These findings suggest that long-term administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal APP processing and decreasing the formation of amyloidogenic APP products.
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PMID:The effect of cholinesterase inhibitors on the secretion of APPS from rat brain cortex. 862 19


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