Melanotropin receptors in the brain are differentially distributed and recognize both corticotropin and alpha-melanocyte stimulating hormone.
Melanotropinergic neurons in the brain may mediate the known modulatory effects of alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) on brain functions including thermoregulation, pituitary regulation, learning and behavior. To determine the distribution of brain melanotropin receptors, we used biologically active [125I]Nle4, D-Phe7-alpha-MSH ([125I]NDP-MSH) for in situ binding and autoradiography in frozen rat brain sections. Specific (alpha-MSH-inhibitable) [125I]NDP-MSH binding sites were distributed in a region-specific pattern, and were present in numerous structures within the septal area, hypothalamus, thalamus, epithalamus, olfactostriatal complex, and midbrain. Each brain structure studied showed a characteristic, reproducible distribution and relative intensity of binding. Receptor peptide selectivity was assessed by comparing the dose-response relationships for inhibition of binding by alpha-MSH, NDP-MSH and ACTH. In all brain structures studied, the 3 peptides gave comparable maximal inhibition of tracer binding, indicating that all detectable binding sites recognized all 3 melanotropins. The respective relative potencies were: NDP-MSH (EC50 = 1.7 +/- 0.6 nM) greater than alpha-MSH (EC50 = 46.9 +/- 11.7 nM) = ACTH. These results provide a preliminary neuroanatomic map of potential target sites for melanotropin actions, and indicate that these sites are capable of recognizing multiple products of the intrinsic melanotropinergic system of the brain.
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JB
Department of Medicine, New England Medical Center, Boston, MA 02111.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism*
D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; C029446:MSH receptor; D000324:Adrenocorticotropic Hormone