alpha-Melanotropin hormone inhibits the binding of [H-3]SCH 23390 to the dopamine D-1 receptor in vitro

We have previously demonstrated that the simultaneous presence of alpha-mel anocyte stimulating hormone (alpha-MSH) and dopamine resulted in a reductio n in cyclic AMP (cAMP) levels in slices containing caudate putamen and accu mbens nuclei as compared to those treated only with dopamine or alpha-MSH. This study was carried out to explore if the interaction between alpha-MSH and dopamine could be explained on the basis of a direct interaction betwee n alpha-MSH and the dopamine D-1 receptor. Saturation curves for [n-methyl- H-3](R)-(+)-8 chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7 -ol hemimaleate ([H-3]SCH 23390) binding in the presence of increasing conc entrations of alpha-MSH were performed. Nonlinear regression in the presenc e of alpha-MSH revealed an increased dissociation constant (K-d). The bindi ng capacity (B-max) was not affected by the peptide. These data suggest an apparent competitive interaction between alpha-MSH and [H-3]SCH 23390 in st riatal membranes on the dopamine D-1 receptor; (K-i = 1.2 x 10(-7) M). The present data show that alpha-MSH could interact with the dopamine D-1 recep tor modulating allosterically the affinity of [H-3]SCH 23390 for the recept or or by causing a change in the lipid environment of the dopamine receptor , resulting in an inhibition of the ligand binding to it. (C) 1998 Elsevier Science B.V. All rights reserved.