Alpha-melanotropin hormone inhibits the binding of [3H]SCH 23390 to the dopamine D1 receptor in vitro.
We have previously demonstrated that the simultaneous presence of alpha-melanocyte stimulating hormone (alpha-MSH) and dopamine resulted in a reduction in cyclic AMP (cAMP) levels in slices containing caudate putamen and accumbens 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 between alpha-MSH and the dopamine D1 receptor. Saturation curves for [n-methyl-3 H](R)-(+)-8 chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1 H-3-benzazepin-7-o] hemimaleate ([3H]SCH 23390) binding in the presence of increasing concentrations of alpha-MSH were performed. Nonlinear regression in the presence of alpha-MSH revealed an increased dissociation constant (Kd). The binding capacity (Bmax) was not affected by the peptide. These data suggest an apparent competitive interaction between alpha-MSH and [3H]SCH 23390 in striatal membranes on the dopamine D1 receptor; (Ki = 1.2 X 10(-7) M). The present data show that alpha-MSH could interact with the dopamine D1 receptor modulating allosterically the affinity of [3H]SCH 23390 for the receptor or by causing a change in the lipid environment of the dopamine receptor, resulting in an inhibition of the ligand binding to it.
Lezcano
N E
NE
Laboratorio de Fisiología, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Salvatierra
N A
NA
Celis
M E
ME
D000818:Animals; D001552:Benzazepines / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium; D000521:alpha-MSH / Q000494:pharmacology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D014316:Tritium; D000521:alpha-MSH; D004298:Dopamine