A calcium fluorescence assay for quantification of cholinergic receptor activity of clinical drugs in serum - comparison with radioactive methods.

Published on Sep 2, 2021in Journal of Pharmacological and Toxicological Methods1.95
· DOI :10.1016/J.VASCN.2021.107118
José N. Nobrega50
Estimated H-index: 50
(U of T: University of Toronto),
Roger Raymond19
Estimated H-index: 19
(CAMH: Centre for Addiction and Mental Health)
+ 1 AuthorsBruce G. Pollock89
Estimated H-index: 89
(U of T: University of Toronto)
Source
Abstract
Abstract null null A new approach is described for quantifying cholinergic receptor activation status human blood samples, based on M1 receptor-driven mobilization of intracellular calcium stores. The assay identifies anticholinergic as well as agonist cholinergic receptor activity. As a cell-based procedure, the assay shares the high efficiency of recently developed M1 receptor binding protocols, but differs from the latter in relying on fluorescence rather than radioactivity measurements. The assay targets a true functional effect insofar as it reflects a time-dependent process of net changes in activation of cholinergic receptors. Results from experiments with M1-expressing CHO cells exposed to a fluorogenic dye and the standard cholinergic agonist carbachol revealed the assay's ability to isolate pure agonist effects of clinical compounds as well as the net effects of serum containing agonist and antagonist factors. The new protocol thus provides two additional quantitative indices of cholinergic receptor activity in human serum, namely pure agonistic effects and net agonist/antagonist effects. As such, it could constitute a very useful addition to efforts to quantify global cholinergic status in human serum in various clinical conditions. By relying on fluorescence measures it should also prove much more accessible than radioactivity-based protocols.
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ABSTRACT Objectives Anticholinergic burden has been associated with deleterious effects on cognition particularly in those with an underlying brain disorder. We developed a new assay based on cultured cells to measure serum anticholinergic activity (cSAA). We report on its relationships with established anticholinergic burden rating scales and cognitive assessments in older patients with mild cognitive impairment (MCI) or major depressive disorder (MDD) in remission or both. Design The study was...
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#1José N. NobregaH-Index: 50
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Abstract Assessments of total anticholinergic activity (SAA) in serum are of considerable interest for its potential involvement in cognitive impairment associated with polydrug states in the elderly and other populations. Such estimations have been based on the displacement of radioligand binding in rat brain tissues. The validity of such measurements has been questioned, as a potentially distorting effect of large serum proteins was identified. We sought to develop a modified assay that would ...
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Increased patients' serum anticholinergic activity (SAA) is described as a marker of cognitive dysfunction and can be influenced by different exogenous and endogenous factors. The role of cortisol in relation to SAA and cognition in perioperative conditions has not been investigated so far. In 30 men scheduled for urological surgery, the authors determined SAA and cortisol levels in blood and CSF and conducted neuropsychological testing in two subgroups with comparable pre- and intraoperative ch...
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