Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system

L Roselli-Rehfuss; K G Mountjoy; L S Robbins; M T Mortrud; M J Low; J B Tatro; M L Entwistle; R B Simerly; R D Cone

doi:10.1073/pnas.90.19.8856

Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system

Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8856-60. doi: 10.1073/pnas.90.19.8856.

Authors

L Roselli-Rehfuss¹, K G Mountjoy, L S Robbins, M T Mortrud, M J Low, J B Tatro, M L Entwistle, R B Simerly, R D Cone

Affiliation

¹ Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.

Abstract

Corticotropin (ACTH) and melanotropin (MSH) peptides (melanocortins) are produced not only in the pituitary but also in the brain, with highest concentrations in the arcuate nucleus of the hypothalamus and the commisural nucleus of the solitary tract. We have identified a receptor for MSH and ACTH peptides that is specifically expressed in regions of the hypothalamus and limbic system. This melanocortin receptor (MC3-R) is found in neurons of the arcuate nucleus known to express proopiomelanocortin (POMC) and in a subset of the nuclei to which these neurons send projections. The MC3-R is 43% identical to the MSH receptor present in melanocytes and is strongly coupled to adenylyl cyclase. Unlike the MSH or ACTH receptors, MC3-R is potently activated by gamma-MSH peptides, POMC products that were named for their amino acid homology with alpha- and beta-MSH, but lack melanotropic activity. The primary biological role of the gamma-MSH peptides is not yet understood. The location and properties of this receptor provide a pharmacological basis for the action of POMC peptides produced in the brain and possibly a specific physiological role for gamma-MSH.

Publication types

Comparative Study

MeSH terms

Adenylyl Cyclases / genetics
Adenylyl Cyclases / metabolism
Adrenocorticotropic Hormone / chemistry
Amino Acid Sequence
Animals
Blotting, Northern
Brain / metabolism*
Cloning, Molecular
Humans
Hypothalamus / metabolism*
In Situ Hybridization
Kinetics
Limbic System / metabolism*
Male
Melanocyte-Stimulating Hormones / chemistry
Melanocyte-Stimulating Hormones / metabolism*
Molecular Sequence Data
Organ Specificity
Polymerase Chain Reaction / methods
Pro-Opiomelanocortin / metabolism*
Prosencephalon / metabolism
RNA, Messenger / analysis
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 3
Receptors, Melanocortin / analysis
Receptors, Melanocortin / chemistry
Receptors, Melanocortin / metabolism*
Receptors, Pituitary Hormone / analysis
Receptors, Pituitary Hormone / chemistry
Receptors, Pituitary Hormone / metabolism*
Recombinant Fusion Proteins / metabolism
Sequence Homology, Amino Acid

Substances

RNA, Messenger
Receptor, Melanocortin, Type 3
Receptors, Melanocortin
Receptors, Pituitary Hormone
Recombinant Fusion Proteins
melanocortin 3 receptor, rat
Pro-Opiomelanocortin
MSH receptor
Adrenocorticotropic Hormone
Melanocyte-Stimulating Hormones
Adenylyl Cyclases

Associated data

GENBANK/X65633
GENBANK/X65634
GENBANK/X65635
GENBANK/X70667