Bitzinger, Diane I. and Gruber, Michael and Tuemmler, Simon and Michels, Bernhard and Bundscherer, Anika and Hopf, Susanne and Trabold, Benedikt and Graf, Bernhard M. and Zausig, York A. (2016) Species- and concentration-dependent differences of acetyl- and butyrylcholinesterase sensitivity to physostigmine and neostigmine. NEUROPHARMACOLOGY, 109. pp. 1-6. ISSN 0028-3908, 1873-7064
Full text not available from this repository. (Request a copy)Abstract
Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a common protocol regarding concentration- and species-dependent differences in inhibitory potency (IC 50) of clinical relevant ChE-Is is still not available. To evaluate the in vitro sensitivity of Acetyl- and Butyrylcholinesterase (AChE, BChE), we compared the concentration-response effects of physostigmine and neostigmine on cholinesterases in whole blood from rat and human. A spectrophotometrical test system based on in vitro Ellman's reagent has been used to determine the kinetic properties of clinical relevant ChE-Is. In vitro, the enzyme activity of human AChE and BChE was inhibited in a concentration-dependent manner until a residual activity of 4-6% for AChE and 20-30% for BChE (IC 50 human AChE: 0.117 +/- 0.007 mu M physostigmine, 0.062 +/- 0.003 mu M neostigmine; IC 50 human BChE: 0373 +/- 0.089 mu M neostigmine; 0.059 +/- 0.012 mu M physostigmine). The inhibition curve of rat BChE in contrast showed no concentration-dependency for physostigmine and neostigmine (87% residual activity even at high inhibitor concentrations). Rat AChE was inhibited in a concentration-dependent manner until a residual activity of 53%. The results suggest that cholinesterases from human and rat show marked species- and inhibitor dependent differences in sensitivity to physostigmine and neostigmine. Knowledge of such differences may be critical in assessing the possible therapeutic effects of ChE-Is in both species and may guide researchers in the optimal design of future experiments regarding the application of ChE-Is. (C) 2016 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHOLINESTERASE-INHIBITORS; BLOOD CHOLINESTERASE; ALZHEIMERS-DISEASE; RAT-BRAIN; ACETYLCHOLINESTERASE; PHARMACOKINETICS; INFLAMMATION; METABOLISM; PARAMETERS; SURVIVAL; Butyrylcholinesterase; Acetylcholinesterase; Alzheimer's disease; Physostigmine; Neostigmine; Inflammatory disease; Rat; Ellman's reagent; Cholinesterase inhibitors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Apr 2019 11:39 |
| Last Modified: | 03 Apr 2019 11:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3265 |
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