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The British Journal of Ophthalmology Dec 1968
Topics: Acetylcholine; Anterior Chamber; Carbachol; Cataract; Cholinesterase Inhibitors; Cysts; Echothiophate Iodide; Glaucoma; Headache; Humans; Isoflurophate; Methacholine Compounds; Miotics; Myopia; Neostigmine; Pain; Parasympathetic Nervous System; Parasympathomimetics; Physostigmine; Pilocarpine; Quaternary Ammonium Compounds; Retinal Detachment; Spasm; Strabismus; Uveitis
PubMed: 5750171
DOI: 10.1136/bjo.52.12.936 -
Experimental Eye Research Jan 2010Accommodation and pupil constriction result from parasympathetic stimulation from the Edinger-Westphal (EW) nucleus of the midbrain resulting in release of acetylcholine...
Accommodation and pupil constriction result from parasympathetic stimulation from the Edinger-Westphal (EW) nucleus of the midbrain resulting in release of acetylcholine at the neuromuscular junctions of the ciliary muscle and iris. Cholinergic and adrenergic drugs can be applied topically to evaluate the effects on the pupil and accommodative system without input from the EW nucleus. This study is directed at characterizing how topical low dose echothiophate, an anti-cholinesterase inhibitor (i.e., an indirect cholinergic agonist), epinephrine, an adrenergic agonist, and timolol maleate, a beta adrenergic antagonist, affect pupil diameter, resting refraction and accommodative amplitude and dynamics in rhesus monkeys. The effects of 0.015% echothiophate, 2% epinephrine, 0.5% timolol maleate and saline on pupil diameter and resting refraction were measured in one eye each of four normal rhesus monkeys for 60-90 min following topical instillation. Pupil diameter was measured with infrared videography and refraction was measured with a Hartinger coincidence refractometer. Effects on static and dynamic EW stimulated accommodation were studied in three iridectomized monkeys (ages 5, 6 and 12 years) with permanent indwelling stimulating electrodes in the EW nucleus. Dynamic accommodative responses were measured with infrared photorefraction for increasing current amplitudes before and during the course of action of the pharmacological agents. Echothiophate caused a significant decrease in pupil diameter of 3.07 +/- 0.65 mm (mean +/- SEM, p < 0.01), and a myopic shift in resting refraction of 1.30 +/- 0.39 D (p < 0.05) 90 min after instillation. Epinephrine caused a 2.76 +/- 0.38 mm (p < 0.01) increase in pupil diameter with no change in resting refraction 60 min after instillation. Timolol maleate resulted in no significant change in either pupil diameter or resting refraction 60 min after instillation. There was no significant change in maximum EW stimulated accommodative amplitude after any agent tested. The amplitude vs. peak velocity relationship for accommodation was significantly different after echothiophate and timolol maleate, and for disaccommodation after echothiophate, epinephrine and timolol maleate. In conclusion, when tested objectively in anesthetized monkeys, epinephrine and timolol maleate did not alter resting refraction or accommodative amplitude, but did have small, significant affects on accommodative dynamics. This suggests that there is an adrenergic component to the accommodative system. Low dose echothiophate had significant effects on pupil diameter and resting refraction, with only small effects on the dynamics of the accommodative response.
Topics: Accommodation, Ocular; Administration, Topical; Adrenergic Agonists; Adrenergic beta-Antagonists; Animals; Autonomic Agents; Autonomic Nervous System; Cholinesterase Inhibitors; Echothiophate Iodide; Epinephrine; Iridectomy; Iris; Macaca mulatta; Pupil; Refraction, Ocular; Timolol; Video Recording
PubMed: 19782072
DOI: 10.1016/j.exer.2009.09.015 -
Molecules (Basel, Switzerland) Mar 2020Enzyme-catalyzed hydrolysis of echothiophate, a P-S bonded organophosphorus (OP) model, was spectrofluorimetrically monitored, using Calbiochem Probe IV as the thiol...
Enzyme-catalyzed hydrolysis of echothiophate, a P-S bonded organophosphorus (OP) model, was spectrofluorimetrically monitored, using Calbiochem Probe IV as the thiol reagent. OP hydrolases were: the G117H mutant of human butyrylcholinesterase capable of hydrolyzing OPs, and a multiple mutant of phosphotriesterase, GG1, designed to hydrolyze a large spectrum of OPs at high rate, including V agents. Molecular modeling of interaction between Probe IV and OP hydrolases (G117H butyrylcholinesterase, GG1, wild types of and phosphotriesterases, and human paraoxonase-1) was performed. The high sensitivity of the method allowed steady-state kinetic analysis of echothiophate hydrolysis by highly purified G117H butyrylcholinesterase concentration as low as 0.85 nM. Hydrolysis was michaelian with = 0.20 ± 0.03 mM and = 5.4 ± 1.6 min. The GG1 phosphotriesterase hydrolyzed echothiophate with a high efficiency ( = 2.6 ± 0.2 mM; = 53400 min). With a = (2.6 ± 1.6) × 10 Mmin, GG1 fulfills the required condition of potential catalytic bioscavengers. quantum mechanics/molecular mechanics (QM/MM) and molecular docking indicate that Probe IV does not interact significantly with the selected phosphotriesterases. Moreover, results on G117H mutant show that Probe IV does not inhibit butyrylcholinesterase. Therefore, Probe IV can be recommended for monitoring hydrolysis of P-S bonded OPs by thiol-free OP hydrolases.
Topics: Biocatalysis; Butyrylcholinesterase; Caulobacteraceae; Echothiophate Iodide; Enzymes; Humans; Hydrolysis; Kinetics; Molecular Docking Simulation; Mutant Proteins; Organophosphorus Compounds; Phosphoric Triester Hydrolases; Spectrometry, Fluorescence; Sulfolobus
PubMed: 32192230
DOI: 10.3390/molecules25061371 -
The British Journal of Ophthalmology Jul 1965
Comparative Study
Topics: Adult; Aged; Echothiophate Iodide; Glaucoma; Humans; Intraocular Pressure; Middle Aged; Pilocarpine; Tonometry, Ocular
PubMed: 5829767
DOI: 10.1136/bjo.49.7.369 -
Transactions of the American... 1966
Comparative Study
Topics: Adult; Aged; Carbachol; Cataract; Cholinesterase Inhibitors; Echothiophate Iodide; Female; Glaucoma; Humans; Isoflurophate; Male; Middle Aged; Parasympathomimetics; Pilocarpine; Quaternary Ammonium Compounds; Retrospective Studies
PubMed: 6007355
DOI: No ID Found -
The British Journal of Ophthalmology Mar 1974
Topics: Abducens Nerve; Child, Preschool; Echothiophate Iodide; Eyeglasses; Fixation, Ocular; Follow-Up Studies; Humans; Infant; Isoflurophate; Methods; Ophthalmoplegia; Prognosis; Strabismus
PubMed: 4834597
DOI: 10.1136/bjo.58.3.240 -
Chemical Research in Toxicology Sep 2019The single residue mutation of butyrylcholinesterase (BChE) hydrolyzes a number of organophosphosphorus (OP) anticholinesterases. Whereas other BChE active site/proximal...
The single residue mutation of butyrylcholinesterase (BChE) hydrolyzes a number of organophosphosphorus (OP) anticholinesterases. Whereas other BChE active site/proximal mutations have been investigated, none are sufficiently active to be prophylactically useful. In a fundamentally different computer simulations driven strategy, we identified a surface peptide loop (residues 278-285) exhibiting dynamic motions during catalysis and modified it via residue insertions. We evaluated these loop mutants using computer simulations, substrate kinetics, resistance to inhibition, and enzyme reactivation assays using both the choline ester and OP substrates. A slight but significant increase in reactivation was noted with paraoxon with one of the mutants, and changes in and catalytic efficiency were noted in others. Simulations suggested weaker interactions between OP versus choline substrates and the active site of all engineered versions of the enzyme. The results indicate that an improvement of OP anticholinesterase hydrolysis through surface loop engineering may be a more effective strategy in an enzyme with higher intrinsic OP compound hydrolase activity.
Topics: Biocatalysis; Butyrylcholinesterase; Catalytic Domain; Cholinesterase Inhibitors; Echothiophate Iodide; Hydrolysis; Isoflurophate; Kinetics; Molecular Dynamics Simulation; Mutation; Paraoxon; Protein Binding; Protein Engineering; Thermodynamics
PubMed: 31411024
DOI: 10.1021/acs.chemrestox.9b00146 -
The Journal of Neuroscience : the... Oct 2011We explored whether nicotinic acetylcholine receptors (nAChRs) might participate in paracrine transmission by asking if they respond to spillover of ACh at a model...
We explored whether nicotinic acetylcholine receptors (nAChRs) might participate in paracrine transmission by asking if they respond to spillover of ACh at a model synapse in the chick ciliary ganglion, where ACh activates diffusely distributed α7- and α3-containing nAChRs (α7-nAChRs and α3*-nAChRs). Elevating quantal content lengthened EPSC decay time and prolonged both the fast (α7-nAChR-mediated) and slow (α3*-nAChR-mediated) components of decay, even in the presence of acetylcholinesterase. Increasing quantal content also prolonged decay times of pharmacologically isolated α7-nAChR- and α3*-nAChR-EPSCs. The effect upon EPSC decay time of changing quantal content was 5-10 times more pronounced for α3*-nAChR- than α7-nAChR-mediated currents and operated over a considerably longer time window: ≈ 20 vs ≈ 2 ms. Control experiments rule out a presynaptic source for the effect. We suggest that α3*-nAChR currents are prolonged at higher quantal content because of ACh spillover and postsynaptic potentiation (Hartzell et al., 1975), while α7-nAChR currents are prolonged probably for other reasons, e.g., increased occupancy of long channel open states. α3*-nAChRs report more spillover when α7-nAChRs are competitively blocked than under native conditions; this could be explained if α7-nAChRs buffer ACh and regulate its availability to activate α3*-nAChRs. Our results suggest that non-α7-nAChRs such as α3*-nAChRs may be suitable for paracrine nicotinic signaling but that α7-nAChRs may not be suitable. Our results further suggest that α7-nAChRs may buffer ACh and regulate its bioavailability.
Topics: Acetylcholine; Aconitine; Anesthetics, Local; Animals; Biophysical Phenomena; Cadmium Chloride; Calcium Channel Blockers; Chick Embryo; Cholinesterase Inhibitors; Conotoxins; Echothiophate Iodide; Excitatory Postsynaptic Potentials; Female; Ganglia, Parasympathetic; Lidocaine; Male; Models, Biological; Neurons; Nicotinic Antagonists; Patch-Clamp Techniques; Protein Subunits; Receptors, Nicotinic; Time Factors; omega-Conotoxin GVIA
PubMed: 22016525
DOI: 10.1523/JNEUROSCI.3400-11.2011