The melanocortin receptor family: MC1R to MC5R

The melanocortin system is one of the most closely studied signalling networks in receptor pharmacology. Five related G-protein-coupled receptors — MC1R through MC5R — respond to melanocortin peptides and coordinate processes ranging from pigmentation to energy balance. Understanding how these subtypes differ sits at the centre of a great deal of peptide research.

A shared architecture

All five are class A GPCRs that couple to Gs, raising intracellular cAMP when activated. They share endogenous agonists derived from proopiomelanocortin (POMC) — the melanocyte-stimulating hormones and ACTH — and are modulated by the antagonists agouti and AgRP. Because one peptide can engage several subtypes, selectivity is a recurring theme in the literature.

MC1R and MC2R

MC1R is expressed in melanocytes and is investigated for its role in pigmentation and the balance between eumelanin and pheomelanin. MC2R is the ACTH receptor, examined in the context of adrenal steroidogenesis; unusually, it responds only to ACTH and not to the MSH peptides.

MC3R and MC4R

Both subtypes are found in the central nervous system and are studied extensively for their roles in energy homeostasis, feeding behaviour and metabolic signalling in research models. MC4R in particular is among the most intensively mapped receptors in metabolic neuroscience.

MC5R and selectivity

MC5R is studied for its role in exocrine gland function and immunomodulation in laboratory models. Because a single analogue can touch multiple receptors, researchers focus heavily on binding selectivity and functional potency. Related compounds supplied by Vela ship as a lyophilised powder for reconstitution with bacteriostatic water, and every batch carries a certificate of analysis.