Alteration of muscarinic acetylcholine receptors in rabies viral-infected dog brains.
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 + or - 2.77 nM) and dumb (n = 6) (6.01 + or - 1.08 nM) types of rabies as compared to 11 controls (2.15 + or - 0.31 nM), whereas the maximum number of receptor sites (B (max)) values were comparable among all subgroups of normal (1.38 + or - 0.10 pmol/mg protein), dumb (1.43 + or - 0.17 pmol/mg protein) and furious (1.28 + or - 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 + or - 3.27 nM), and low (FAT-negative and PCR-positive; n = 4) virus amount (8.34 + or - 3.93 nM) but these were significantly higher than controls (n = 4) (1.58 + or - 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.
Dumrongphol
H
H
Neuro and Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Thailand.
Srikiatkhachorn
A
A
Hemachudha
T
T
Kotchabhakdi
N
N
Govitrapong
P
P
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D004279:DNA, Viral / Q000032:analysis; D004285:Dogs; D004587:Electrophoresis, Agar Gel; D006624:Hippocampus / Q000737:chemistry* / Q000821:virology*; D008024:Ligands; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000494:pharmacology; D011818:Rabies / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000032:analysis / Q000378:metabolism*; D014316:Tritium
D004279:DNA, Viral; D008024:Ligands; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate