Molecular cloning of a mouse melanocortin 5 receptor gene widely expressed in peripheral tissues.
Labbé. O O; Desarnaud. F F; Eggerickx. D D; Vassart. G G; Parmentier. M M
Key Findings
- The MC5 receptor (MC5R) gene was identified and encodes a typical G‑protein‑coupled receptor with multiple glycosylation and phosphorylation sites.
- MC5R is widely expressed in peripheral tissues including skin, muscle, adrenal gland, bone marrow, spleen, thymus, gonads, uterus, and brain.
- The receptor binds alpha‑MSH and synthetic analogs (like NDP‑MSH) with high affinity (Kd ~1.5 nM) and stimulates cAMP production, indicating functional signaling.
Practical Outcomes
- Because MC5R is present in many organs, using melanotan‑I could have effects beyond skin tanning, potentially influencing metabolism, muscle function, or immune responses. However, the study provides no dosage or safety data, so biohackers should treat any systemic use as experimental and proceed with caution.
Summary
Scientists cloned a mouse version of the MC5 receptor, which is a protein that responds to melanocortin peptides like alpha‑MSH (the natural hormone that melanotan‑I mimics). This receptor is found in many body parts—not just skin—such as muscle, adrenal gland, bone marrow and brain, and it activates cellular signaling pathways when it binds the hormone.
Abstract
A mouse genomic clone named HGMP01B has been isolated by homology screening with a probe representing part of the human melanocortin 3 receptor gene. HGMP01B was found to encode a 325 amino acid protein with all the landmarks of G-protein-coupled receptors and belonging to the growing melanocortin receptor family. This receptor displays four potential sites for N-linked glycosylation and five potential sites of phosphorylation by protein kinase C. The HGMP01B gene was found to be expressed in many tissues, including skin, adrenal gland, skeletal muscle, bone marrow, spleen, thymus, gonads, uterus, and brain. A stable Chinese hamster ovary (CHO) cell line expressing approximately 10,000 receptors per cell was established. This cell line displayed a saturable binding capacity for the radioiodinated alpha-melanocyte-stimulating hormone (alpha-MSH) analog [Nle4,D-Phe7]-alpha-MSH (NDP-MSH) with an apparent Kd of 1.47 +/- 0.15 nM. Binding of the labeled ligand was competed for by all melanocortin peptides, except beta-endorphin or corticotropin-like intermediate lobe peptide (CLIP). NDP-MSH was the most powerful competitor, followed by alpha-MSH, adrenocorticotropic hormone (ACTH), beta-MSH, the gamma-MSHs, and ACTH 4-10. Functional assays confirmed that HGMP01B, like other melanocortin receptors, stimulated adenylyl cyclase. The potency order obtained in these cyclic adenosine monophosphate (cAMP) accumulation assays was consistent with that of the binding studies. HGMP01B therefore appears as a fifth melanocortin receptor (MC5), responding mainly to alpha-MSH (EC50 = 1.07 +/- 0.13 nM) and endowed with a pharmacological profile similar to that of the melanocyte MSH (MC1) receptor, but characterized by a broad tissue distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
Study Information
pubmed
1994
1994-04-19T00:00:00.000Z
10.1021/bi00181a015