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The Biochemical Journal May 1959
Topics: Acetylcholine; Animals; Brain; Choline O-Acetyltransferase; Columbidae; Esterases; Rats; Synaptic Transmission
PubMed: 13651154
DOI: 10.1042/bj0720165 -
Korean Journal of Ophthalmology : KJO Dec 1994We performed a randomized, prospective study to evaluate the effect of intraoperative, intracameral carbachol or acetylcholine on early postoperative intraocular... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
We performed a randomized, prospective study to evaluate the effect of intraoperative, intracameral carbachol or acetylcholine on early postoperative intraocular pressure(IOP) after extracapsular cataract extraction(ECCE) and posterior chamber lens(PCL) implantation. Fifty-six eyes of 56 patients scheduled for routine ECCE and PCL implantation were randomly assigned into three groups: (1)carbachol infusion (19 eyes) (2) acetylcholine infusion (15 eyes) (3)balanced salt solution (BSS) infusion (control, 22 eyes). We compared the preoperative IOP, early postoperative IOP, postoperative 24 hours IOP and postoperative 1 week IOP. In the measurement of early postoperative IOP, IOP was measured at least twice at 3, 6 or 9 hours postoperatively. There was no significant difference in IOP between the three groups preoperatively, at postoperative 3 hours, and 1 week. At postoperative 6 hours, both the carbachol infusion group and acetylcholine infusion group were significantly different from the BSS infusion group. At postoperative 9 and 24 hours, only carbachol infusion group had a significant difference from BSS infusion group in suppression of postoperative IOP increase. Our results suggest that intraoperative, intracameral administration of carbachol or acetylcholine prevents early postoperative IOP increase, and that carbachol has a more lasting effect.
Topics: Acetylcholine; Adult; Aged; Anterior Chamber; Carbachol; Cataract Extraction; Female; Humans; Intraocular Pressure; Lenses, Intraocular; Male; Middle Aged; Ocular Hypertension; Postoperative Complications; Prospective Studies
PubMed: 7853733
DOI: 10.3341/kjo.1994.8.2.61 -
The Journal of Physiology Jan 19701. Segments of rat diaphragms were kept in choline-free media for 4 hr and were then exposed to a physiological concentration of [(14)C]-choline (30 muM) at 37 degrees...
1. Segments of rat diaphragms were kept in choline-free media for 4 hr and were then exposed to a physiological concentration of [(14)C]-choline (30 muM) at 37 degrees C. The synthesis, storage and subsequent release of [(14)C]acetylcholine by the muscles was assessed by isotopic- and bio-assays after isolation of the transmitter by paper electrophoresis.2. Replacement of endogenous acetylcholine (0.92 mu-mole/kg) with labelled acetylcholine proceeded slowly at rest, but rapidly during nerve stimulation. [(14)C]Acetylcholine accumulated most rapidly when hydrolysis of the released transmitter, and thus the re-use of endogenous choline, was prevented by an esterase inhibitor. Fully replaced stores were maintained during nerve stimulation by synthesis rates sufficient to replenish at least 35% of the store size in 5 min.3 In the presence of hemicholinium-3, which inhibits choline uptake, acetylcholine stores declined rapidly during stimulation, and residual synthesis was slight, indicating little intraneural choline. Net choline uptake into nerve terminals was estimated from the highest observed synthesis rate and from previous measurements of the number and size of terminals, as 3-6 p-mole/cm(2) sec.4. Transmitter synthesis was localized in the region of end-plates, and was reduced to a few per cent of normal 6 weeks after phrenic nerve section. Release experiments suggested that at least half of the acetylcholine in phrenic nerves is in their terminals; from this content and the morphology of the terminals, the average concentration of transmitter in the whole endings would appear to be about 50 m-mole/l. Homogenization of the muscles freed choline acetyltransferase into solution, but left some [(14)C]acetylcholine associated with small particles, presumably synaptic vesicles.5. Resting transmitter release was about 0.013% of stores/sec. With 360 nerve impulses at 1-20/sec, release increased up to 0.43% of stores/sec, and amounted to 3.5-7 x 10(-18) moles per end-plate per impulse. The release rate was unaffected by the doubling of store size which occurred with eserine, but the extra transmitter did help to maintain releasable stores during prolonged stimulation. Experiments with fractional store labelling indicated that newly synthesized acetylcholine was preferentially released.6. Preformed [(3)H]acetylcholine was not taken up and retained by muscle or nerve cells in the absence of an esterase inhibitor. With eserine present, labelled acetylcholine was taken up uniformly by muscle segments; when eserine was then removed, radioactive acetylcholine remained only near neuromuscular junctions.
Topics: Acetylcholine; Acyltransferases; Animals; Carbon Isotopes; Choline; Diaphragm
PubMed: 5498453
DOI: 10.1113/jphysiol.1970.sp009003 -
British Journal of Pharmacology Jul 19741 Measurements have been made of the osmotic coefficients and enthalpies of dilution of acetylcholine and of compounds related to it in which the carbonyl and ether...
Physicochemical properties and biological activity: thermodynamic properties of compounds related to acetylcholine assessed from depression of freezing-point and enthalpies of dilution.
1 Measurements have been made of the osmotic coefficients and enthalpies of dilution of acetylcholine and of compounds related to it in which the carbonyl and ether groups have been replaced by methylene and the trimethylammonium group by triethylammonium. All were iodides. Measurements were also made with tetraethylammonium iodide and agree with published values.2 Where necessary the affinities of the compounds for acetylcholine receptors in the guinea-pig ileum and frog rectus, or their activities relative to acetylcholine, have been measured.3 The osmotic coefficients were used to calculate activity coefficients and excess free energies, which have been used with the excess enthalpies to calculate the excess entropies of the solutions. These indicate that the ester and carbonyl groups have a marked ordering effect on the ions in water compared with methylene groups; the ether group has an intermediate effect.4 When the results are interpreted in terms of ion-pair formation they can be used to calculate the ion-association constants and enthalpies and entropies of formation of ion-pairs, and lead to similar conclusions: that the order associated with ion-pair formation is greater with the esters and ketones. There appears to be extensive ion-association in the concentrations (0.5 to 1M) usually used in n.m.r. studies.5 There is no obvious correlation between the effects of groups on water and their activity or affinity at muscarine-sensitive acetylcholine receptors but it is possible that ability to activate nicotine-sensitive receptors may be associated with an increase in order, though it would be necessary to study entropy changes in systems actually involving receptors in order to prove this. It is also necessary to suppose that ability to activate these receptors is limited to compounds with small onium groups.
Topics: Acetylcholine; Animals; Anura; Calorimetry; Chemical Phenomena; Chemistry; Dose-Response Relationship, Drug; Esters; Guinea Pigs; Ileum; In Vitro Techniques; Iodides; Ketones; Mathematics; Osmolar Concentration; Quaternary Ammonium Compounds; Rectum; Structure-Activity Relationship; Thermodynamics
PubMed: 4451755
DOI: 10.1111/j.1476-5381.1974.tb10677.x -
British Journal of Pharmacology Jan 19711. The effects of oxotremorine on the guinea-pig ileum have been investigated to determine whether any component of its action is due to acetylcholine release.2. Log...
1. The effects of oxotremorine on the guinea-pig ileum have been investigated to determine whether any component of its action is due to acetylcholine release.2. Log dose-response curves to oxotremorine and acetylcholine were similar and both drugs were competitively antagonized by atropine.3. Mipafox potentiated acetylcholine but not oxotremorine.4. No evidence of an indirect component of the action of oxotremorine was obtained using various pharmacological procedures (tetrodotoxin, morphine, cooling, procaine and hemicholinium-3).5. Oxotremorine had no effect on acetylcholine release from mipafox treated ileum but decreased the release from physostigmine treated ileum.6. It is concluded that oxotremorine acts directly on muscarinic receptors and not by releasing acetylcholine.
Topics: Acetylcholine; Amides; Animals; Atropine; Cholinesterase Inhibitors; Drug Synergism; Guinea Pigs; Hemicholinium 3; Ileum; In Vitro Techniques; Morphine; Muscle, Smooth; Phosphoric Acids; Procaine; Pyrrolidinones; Receptors, Drug; Secretory Rate; Tetrodotoxin
PubMed: 5547759
DOI: 10.1111/j.1476-5381.1971.tb09931.x -
Basic Research in Cardiology Jan 2022Endothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate...
Endothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate diabetic vasculopathy. As an alternative to oxidative stress-induced dysfunction, we interrogated if impaired mitochondrial function in endothelial cells is central to endothelial dysfunction in the metabolic syndrome. We observed reduced coronary arteriolar vasodilation to the endothelium-dependent dilator, acetylcholine (Ach), in Zucker Obese Fatty rats (ZOF, 34 ± 15% [mean ± standard deviation] 10 M) compared to Zucker Lean rats (ZLN, 98 ± 11%). This reduction in dilation occurred concomitantly with mitochondrial DNA (mtDNA) strand lesions and reduced mitochondrial complex activities in the endothelium of ZOF versus ZLN. To demonstrate endothelial dysfunction is linked to impaired mitochondrial function, administration of a cell-permeable, mitochondria-directed endonuclease (mt-tat-EndoIII), to repair oxidatively modified DNA in ZOF, restored mitochondrial function and vasodilation to Ach (94 ± 13%). Conversely, administration of a cell-permeable, mitochondria-directed exonuclease (mt-tat-ExoIII) produced mtDNA strand breaks in ZLN, reduced mitochondrial complex activities and vasodilation to Ach in ZLN (42 ± 16%). To demonstrate that mitochondrial function is central to endothelium-dependent vasodilation, we introduced (via electroporation) liver mitochondria (from ZLN) into the endothelium of a mesenteric vessel from ZOF and restored endothelium-dependent dilation to vasoactive intestinal peptide (VIP at 10 M, 4 ± 3% vasodilation before mitochondrial transfer and 48 ± 36% after transfer). Finally, to demonstrate mitochondrial function is key to endothelium-dependent dilation, we administered oligomycin (mitochondrial ATP synthase inhibitor) and observed a reduction in endothelium-dependent dilation. We conclude that mitochondrial function is critical for endothelium-dependent vasodilation.
Topics: Acetylcholine; Animals; DNA, Mitochondrial; Endothelial Cells; Endothelium, Vascular; Metabolic Syndrome; Mitochondria; Rats; Rats, Zucker; Vasodilation
PubMed: 35039940
DOI: 10.1007/s00395-021-00908-1 -
British Journal of Pharmacology Jul 19711. The relationship between the capacity of the chick biventer preparation, both intact tissue and homogenate, to inactivate acetylcholine and the ability of eserine to...
1. The relationship between the capacity of the chick biventer preparation, both intact tissue and homogenate, to inactivate acetylcholine and the ability of eserine to increase the sensitivity of the tissue to acetylcholine have been investigated.2. At concentrations of eserine of 2.69 x 10(-9)M and 2.69 x 10(-8)M the capacity of the whole tissue to inactivate acetylcholine is reduced by 5% and 15% respectively. These concentrations of eserine increase the sensitivity of the preparation to acetylcholine by factors of 2 and 4 respectively, without a change of slope in regression lines.3. At concentrations of eserine of 2.69 x 10(-7)M and 2.69 x 10(-6)M the capacity of the whole tissue to inactivate acetylcholine is reduced by 40% and 80% respectively, and the sensitivity to acetylcholine increased by factors of 70 and 800 respectively, along with marked increases in the slopes of the regression lines.4. An attempt has been made to quantify these differences by proposing a model in which cholinesterase in the tissue is regarded as a network, preventing the access of a large fraction of the acetylcholine to its site of action.5. It is suggested that, whereas the increase in sensitivity to acetylcholine at eserine concentrations of 2.69 x 10(-9)M and 2.69 x 10(-8)M can be interpreted as an anticholinesterase effect (which is still present at higher concentrations), that seen at the higher concentrations may represent a direct action of eserine on the tissue.6. It is further suggested that there are barriers to penetration in intact tissue to both substrate and inhibitor, which invalidate attempts to extrapolate results from homogenates.
Topics: Acetylcholine; Animals; Biological Assay; Carbachol; Chickens; Cholinesterases; Decamethonium Compounds; Ileum; In Vitro Techniques; Male; Models, Biological; Muscles; Physostigmine; Succinylcholine
PubMed: 5560900
DOI: 10.1111/j.1476-5381.1971.tb07126.x -
Molecules (Basel, Switzerland) Feb 2020Acetylcholine, which is associated with Alzheimer's disease, is widely known to have conformers. The preference of each conformer to undergo neutral hydrolysis is yet to...
Acetylcholine, which is associated with Alzheimer's disease, is widely known to have conformers. The preference of each conformer to undergo neutral hydrolysis is yet to be considered. In this study, we employed density-functional calculations to build the conformers and investigated their preference in one-step neutral hydrolysis. The results showed the preference in ten possible hydrolysis pathways involving seven acetylcholine conformers (reactant), four transition state structures, and two choline conformers (product). Three out of the seven acetylcholine conformers predicted from the results confirmed experimental findings on the conformers stability. We suggested that two out of ten possible pathways were observed in the experimental results based on agreement in reaction energy. Eventually, this study will emphasize the importance of considering acetylcholine conformers in its hydrolysis study.
Topics: Acetylcholine; Alzheimer Disease; Density Functional Theory; Humans; Hydrogen Bonding; Hydrolysis; Molecular Conformation; Neurotransmitter Agents; Synaptic Transmission; Thermodynamics
PubMed: 32033277
DOI: 10.3390/molecules25030670 -
Cell Reports Feb 2024The ability of the mammalian brain to maintain spatial representations of external or internal information for short periods of time has been associated with sustained...
The ability of the mammalian brain to maintain spatial representations of external or internal information for short periods of time has been associated with sustained neuronal spiking and reverberatory neural network activity in the medial entorhinal cortex. Here, we show that conditional genetic deletion of netrin-1 or the netrin receptor deleted-in-colorectal cancer (DCC) from forebrain excitatory neurons leads to deficits in short-term spatial memory. We then demonstrate that conditional deletion of either netrin-1 or DCC inhibits cholinergic persistent firing and show that cholinergic activation of muscarinic receptors expressed by entorhinal cortical neurons promotes persistent firing by recruiting DCC to the plasma membrane. Together, these findings indicate that normal short-term spatial memory function requires the synergistic actions of acetylcholine and netrin-1.
Topics: Animals; Acetylcholine; Netrin-1; Entorhinal Cortex; Prosencephalon; Cholinergic Agents; Mammals
PubMed: 38377003
DOI: 10.1016/j.celrep.2024.113812 -
Analytical Chemistry Aug 2009Two electrocatalytic enzyme modified microelectrode systems were employed as end-column amperometric detectors of choline (Ch) and acetylcholine (ACh) following...
Two electrocatalytic enzyme modified microelectrode systems were employed as end-column amperometric detectors of choline (Ch) and acetylcholine (ACh) following separation by capillary electrophoresis (CE). Horseradish peroxidase cross-linked in an osmium based redox polymer hydrogel (HRP-Os) was physically adsorbed on Au microelectrodes followed by chemical cross-linking of the enzymes acetylcholinesterase (AChE) and choline oxidase (ChO). An alternative approach utilized the deposition of the transition metal catalyst, Prussian Blue (PB), on Pt microelectrodes as the electrocatalyst. Utilizing butyrylcholine (BuCh) as an internal standard, the HRP-Os/AChE-ChO and PB/AChE-ChO electrodes exhibited excellent linear responses from 2-2000 microM and 10-2000 microM, respectively, for both Ch and ACh. Detection limits of 0.1 microM or 38 amol were determined for the HRP-Os/AChE-ChO electrode. The limit of detection for ACh and Ch at the PB/AChE-ChO electrode was 5 microM or 9.5 fmol. The electrodes were operated at potentials of +0.10 and -0.10 V vs Ag/AgCl (3 M NaCl), respectively, and thus minimized the potential response from oxidizable interferences. In addition, both electrocatalytic electrodes showed good operational stability for more than 70 h. The enhanced detection capability of the HRP-Os/AChE-ChO and PB/AChE-ChO electrodes in combination with efficient CE separation of Ch and ACh provides a new sensitive and selective strategy for monitoring and quantifying these cholinergic biomarkers in biological fluids.
Topics: Acetylcholine; Acetylcholinesterase; Alcohol Oxidoreductases; Catalysis; Choline; Electrochemistry; Electrophoresis, Capillary; Enzyme Stability; Enzymes, Immobilized; Limit of Detection; Microelectrodes; Oxidation-Reduction; Reference Standards
PubMed: 20337384
DOI: 10.1021/ac9010843