TY - JOUR
T1 - [3H]GBR‐12935 Binding to the Dopamine Transporter Is Decreased in the Caudate Nucleus in Parkinson's Disease
AU - Janowsky, Aaron
AU - Vocci, Frank
AU - Berger, Paul
AU - Angel, Itzchak
AU - Zelnik, Nethanel
AU - Kleinman, Joel E.
AU - Skolnick, Phil
AU - Paul, Steven M.
PY - 1987/8
Y1 - 1987/8
N2 - The specific binding of [3H]GBR‐12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (KD 2.34 ± 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (20%) decrease in specific [3H]GBR‐12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r= 0.98; p < 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR‐12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r= 0.96; p < 0.01). The specific binding of [3H]GBR‐12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age‐and sex‐matched controls. These data suggest that [3H]GBR‐12935 binds in a sodium‐dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.
AB - The specific binding of [3H]GBR‐12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 ± 0.18 pmol/mg protein), sodium dependent, and of high affinity (KD 2.34 ± 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (20%) decrease in specific [3H]GBR‐12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r= 0.98; p < 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR‐12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r= 0.96; p < 0.01). The specific binding of [3H]GBR‐12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age‐and sex‐matched controls. These data suggest that [3H]GBR‐12935 binds in a sodium‐dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.
KW - Caudate nucleus
KW - Dopamine transport complex
KW - Parkinson's disease
KW - [H]GBR‐12935
UR - http://www.scopus.com/inward/record.url?scp=0023161727&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.1987.tb02908.x
DO - 10.1111/j.1471-4159.1987.tb02908.x
M3 - Article
C2 - 3598589
AN - SCOPUS:0023161727
SN - 0022-3042
VL - 49
SP - 617
EP - 621
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -