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Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients
Author(s) -
Ahlskog J. Eric,
Richelson Elliott,
Nelson Albert,
Kelly Patrick J.,
Okazaki Haruo,
Tyce Gertrude M.,
van Heerden Jon A.,
Stoddard Susan L.,
Carmichael Stephen W.
Publication year - 1991
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410300210
Subject(s) - muscarinic acetylcholine receptor , muscarinic acetylcholine receptor m4 , quinuclidinyl benzilate , medicine , endocrinology , levodopa , dopamine receptor , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m2 , dopamine receptor d2 , muscarinic acetylcholine receptor m3 , caudate nucleus , dopamine , receptor , psychology , chemistry , parkinson's disease , disease
Binding of spiperone and 3‐quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 ( 3 H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was a clinically homogeneous group of patients: All remained predominantly responsive to levodopa, although with Marchked disability secondary to clinical fluctuations (short‐duration responses) and medication‐induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [ 3 H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This finding may reflect medication‐induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [ 3 H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergick cells, inferred to be present based on the prominent levodopa‐induced dyskinesias. Finally, receptor deficits could have also been a reflection of more widespread degenerative cerebral disease, although levodopa‐refractory symptoms were generally not pronounced in these patients.