α-Melanotropin hormone inhibits the binding of [3H]SCH 23390 to the dopamine D1 receptor in vitro

• Published in: European journal of pharmacology 1998-12, Vol.363 (2-3), p.211-215
• Main Authors: LEZCANO, N. E, SALVATIERRA, N. A, CELIS, M. E
• Format: Article
• Language: English
• Subjects: alpha-MSH - pharmacology; Animals; Benzazepines - metabolism; Benzazepines - pharmacology; Binding, Competitive - drug effects; Biological and medical sciences; Cell Membrane - drug effects; Cell Membrane - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; In Vitro Techniques; Male; Rats; Rats, Wistar; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - metabolism; Synaptosomes - drug effects; Synaptosomes - metabolism; Tritium; Vertebrates: endocrinology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00772-9

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.