Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients.
Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked 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 [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]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 cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.
Ahlskog
J E
JE
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Richelson
E
E
Nelson
A
A
Kelly
P J
PJ
Okazaki
H
H
Tyce
G M
GM
van Heerden
J A
JA
Stoddard
S L
SL
Carmichael
S W
SW
D000328:Adult; D016380:Brain Tissue Transplantation; D001971:Bromocriptine / Q000627:therapeutic use; D002421:Caudate Nucleus / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D010479:Pergolide / Q000627:therapeutic use; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics; D011950:Receptors, Cholinergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013134:Spiperone / Q000493:pharmacokinetics
D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D010479:Pergolide; D001971:Bromocriptine; D007980:Levodopa; D013134:Spiperone; D011813:Quinuclidinyl Benzilate