A consideration of the dopamine D2 receptor monomer-dimer equilibrium and the anomalous binding properties of the dopamine D2 receptor ligand, N-methyl spiperone
J. Logan et al., A consideration of the dopamine D2 receptor monomer-dimer equilibrium and the anomalous binding properties of the dopamine D2 receptor ligand, N-methyl spiperone, J NEURAL TR, 108(3), 2001, pp. 279-286
Some discrepancies between experimental results with the two D2 antagonists
N-methyl spiperone (NMSP) and raclopride (RAC) have been observed. Among t
hese are the observation that MK-801 increases NMSP binding but not RAC bin
ding; pretreatment with reserpine increases RAC binding but decreases NMSP
binding; and that the two ligands yield different: values for Bmax. It has
been observed that the D2 receptor can exist in both a monomer and dimer fo
rm and that a NMSP photolabel ligand binds primarily to the monomer form wh
ile a RAG-like photolabel ligand binds both. Using a model of the dimerizat
ion in which the equilibrium dissociation constant increases with increasin
g dopamine (DA) concentration, the free monomer concentration can be shown
to go through a maximum value with increasing DA. Using this model with dat
a from a baboon PET study, it can be shown that under certain conditions an
increase in binding could be observed. Further research may show that ther
e are clusters of D2 receptors forming oligomers with more than two recepto
rs in which NMSP binds to more sites on clusters with fewer receptors. If i
ncreasing DA favors cluster with fewer receptors, an increase in NMSP bindi
ng sites may also occur under some circumstances with an increase in DA.