Alteration of muscarinic acetylcholine receptors in rabies viral-infected dog brains

Abstract

Functions of the muscarinic acetylcholine receptor (mAChR) were studied in rabid dog brains using [3H]quinuclidinyl benzilate (QNB) as a radioligand. Of various brain regions, hippocampus and brainstem were the areas mostly affected in terms of impaired specific binding to [3H]QNB, as compared to other regions, as well as to those of controls. Saturation studies of the hippocampus revealed significantly elevated dissociation equilibrium constant (K(d)) values in both furious (n = 5) (9.80 ± 2.77 nM) and dumb (n = 6) (6.01 ± 1.08 nM) types of rabies as compared to 11 controls (2.15 ± 0.31 nM), whereas the maximum number of receptor sites (B(max)) values were comparable among all subgroups of normal (1.38 ± 0.10 pmol/mg protein), dumb (1.43 ± 0.17 pmol/mg protein) and furious (1.28 ± 0.12 pmol/mg protein) rabies types. Hippocampal K(d) values were comparable between high (fluorescent antibody test-FAT and polymerase chain reaction-PCR positive; n = 4) (7.47 ± 3.27 nM), and low (FAT-negative and PCR-positive; n = 4) virus amount (8.34 ± 3.93 nM) but these were significantly higher than controls (n = 4) (1.58 ± 0.17 nM). Our data suggest a functional derangement of mAChR at specific sites of hippocampus and brainstem which is not dependent on the amount of virus.