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/lp/american-medical-association/alteration-of-acetylcholine-synthesis-by-pilocarpine-in-vivo-and-in-9f6pUY9dbg
- Publisher
- American Medical Association
- Copyright
- Copyright © 1984 American Medical Association. All Rights Reserved.
- ISSN
- 0003-9950
- eISSN
- 1538-3687
- DOI
- 10.1001/archopht.1984.01040031262032
- Publisher site
- See Article on Publisher Site
Abstract
Abstract • Imidazole activates synthesis of acetylcholine by choline acetyltransferase. Pilocarpine hydrochloride, an imidazole derivative, was investigated for its activation effect. In vitro, millimolar concentrations of pilocarpine significantly activated human ciliary body and retinal and rabbit corneal epithelial, iris—ciliary body, and retinal choline acetyltransferases. Concentrations greater than 100mM pilocarpine inhibited acetylcholine synthesis. In vivo, 1% or 4% pilocarpine eyedrops given every 30 minutes for four applications failed to significantly alter rabbit ocular acetylcholine levels. There was a tendency for pilocarpine-treated eyes to have lower levels of acetylcholine. Although pilocarpine altered acetylcholine synthesis by human and rabbit ocular tissues in vitro, this phenomenon could not be demonstrated in rabbits in vivo. However, because tissues of intact rabbit eyes degrade pilocarpine, the possibility remains that this drug can alter acetylcholine synthesis when applied to the intact human eye. References 1. White HL, Cavallito CJ: Choline acetyltransferase: Enzyme mechanism and mode of inhibition of a styrylpyridine analogue . Biochim Biophys Acta 1970;206:343-358.Crossref 2. Chao L-P, Wolfgram F: Activation, inhibition and aggregation of choline acetyltransferase (EC2.3.1.6) . J Neurochem 1974;23:697-701.Crossref 3. Moritoki H, Morita M, Kanbe T: Effects of methylxanthines and imidazole on the contractions of guinea-pig ileum induced by transmural stimulation . Eur J Pharmacol 1976;35:185-198.Crossref 4. Ribeiro JA, Dominguez ML, Sa-Aimeida AM, et al: The effects of imidazole in neuromuscular transmission and on synaptosomal calcium uptake in the rat . Arch Int Pharmacodyn Ther 1981;251:270-284. 5. Mindel JS, Mittag TW: Choline acetyltransferase in ocular tissues of rabbits, cats, cattle, and man . Invest Ophthalmol Vis Sci 1976;15:808-814. 6. Barker LA, Dowdall MJ, Whittaker VP: Choline metabolism in the cerebral cortex of guinea pigs . Biochem J 1972;130:1063-1080. 7. Mindel JS, Szilagyi PIA, Zadunaisky JA, et al: The effects of blepharorrhaphy induced depression of corneal cholinergic activity . Exp Eye Res 1979;29:463-468.Crossref 8. Mautner HG: Choline acetyltransferase . CRC Crit Rev Biochem 1977;4:341-370.Crossref 9. Burt AM, Silver A: A non-enzymatic imidazole-catalyzed acyl transfer reaction and acetylcholine synthesis . Nature 1973;243:157-159. 10. Fonnum F, Malthe-Sorensen D: Membrane affinities and subcellular distribution of the different molecular forms of choline acetyltransferase from rat . J Neurochem 1973;20:1351-1359.Crossref 11. White HL, Wu JC: Separation of apparent multiple forms of human brain choline acetyltransferase by isoelectric focusing . J Neurochem 1973;21:939-947.Crossref 12. Benishin CG, Carroll PT: Multiple forms of choline-O-acetyltransferase in mouse and rat brain: Solubilization and characterization . J Neurochem 1983;41:1030-1039.Crossref 13. Chao L-P, Wolfgram F: Activation, inhibition and aggregation of choline acetyltransferase . J Neurochem 1974;23:679-701.Crossref 14. Hersh LB, Wainer BH, Andrews LP: Multiple isoelectric and molecular weight variants of choline acetyltransferase—artifact or real? J Biol Chem 1984;259:1253-1258. 15. Morris D, Maneckjee A, Hebb C: The kinetic properties of human placental choline acetyltransferase . Biochem J 1971;125:857-863. 16. Ryan R, McClure WO: Physical and kinetic properties of choline acetyl transferase from rat and bovine brain . J Neurochem 1980;34:395-403.Crossref 17. Chrai SS, Robinson JR: Corneal permeation of topical pilocarpine nitrate in the rabbit . Am J Ophthalmol 1974;77:735-739. 18. Lee VH, Hui HW, Robinson JR: Corneal metabolism of pilocarpine in pigmented rabbits . Invest Ophthalmol Vis Sci 1980;19:210-213.
Journal
Archives of Ophthalmology – American Medical Association
Published: Oct 1, 1984