We report the isolation of a gene encoding a novel member of the family of melanocortin receptors. The mouse melanocortin-5 receptor (mMC5R) responds to melanocortins with an increase in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) concentrations. Stimulation of the mMC5R by the melanocortins revealed a hierarchy of potency in which alpha-melanocyte stimulating hormone (alpha-MSH) > beta-melanocyte stimulating hormone (beta-MSH) > adrenocorticotropic hormone (ACTH) > gamma- melanocyte stimulating hormone (gamma-MSH). Further structure-activity studies indicated that amino- and carboxyl-terminal portions of alpha-MSH appear to be key determinants in the activation of mMC5R whereas the melanocortin core heptapeptide sequence is devoid of pharmacological activity. Northern blot analysis demonstrated the expression of mMC5R mRNA in mouse skeletal muscle, lung, spleen, and brain.

Peptide alpha amidation is required to produce some hormones, such as gastrin, from their glycine-extended precursors. This terminal posttranslational processing reaction is thought to be essential for the biological activation of many peptide hormones; only amidated gastrin exerts a physiological effect that results in gastric acid secretion. However, both amidated gastrin and glycine-extended gastrin stimulate proliferation of exocrine pancreatic cell line AR4-2J through selective receptors for the substrate and the product, respectively, of peptide alpha amidation. Thus, the amidation reaction may function as a determinant of the specific biological actions of products derived from prohormones.

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Margaret Chan, Director-General of the WHO, and the heads of seven other global health agencies, call for a concerted global effort to collect better health data.