In general, antagonist affinities for a given receptor subtype have been considered to be constant, regardless of the cell/tissue background in which the receptor is present. Recently, however, this assumption has been challenged with the observation of different pharmacological profiles for the same gene product in different cells/tissues. Anisuzzaman et al. investigated this assumption by evaluating differences in the muscarinic acetylcholine receptor (mAChR) phenotypes present in intact cortex tissue segments compared with the same receptors present in homogenates. The density of mAChRs was similar in both intact tissues and homogenate; however, there was a significant difference in the binding affinity between intact tissue and homogenates. Muscarinic receptor subtype specificity could be observed in homogenates, but in the intact tissue there was a reduced selectivity for M3 antagonists in which the M3 receptor could not be distinguished from other subtypes. This study demonstrates that under conditions that maintain tissue integrity, there is a wide variation in the binding affinity to mAChR subtypes, that there exists an atypical M3 phenotype in the cerebral cortex, and that the pharmacological properties of mAChRs may be significantly modified by tissue integrity and tissue type.
See article at J Pharmacol Exp Ther 2011, 339:186–193.
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