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Molecular Cloning and Characterisation of the Rat Fifth Melanocortin Receptor

1994; Elsevier BV; Volume: 200; Issue: 2 Linguagem: Inglês

10.1006/bbrc.1994.1550

1090-2104

Nathalie Griffon, Virginie Mignon, Patricia Facchinetti, Jorge Díaz, J. Schwartz, Pierre Sokoloff,

Biochemical Analysis and Sensing Techniques

Adrenocorticotropic hormone (ACTH) and melanocortin peptides (α, β and γMSH) have numerous activities in both central nervous system and peripheral tissues, namely the adrenals. Recently, five melanocortin receptors were cloned and characterized. We report here the cloning, pharmacological characterization and expression of the rat fifth melanocortin receptor (MC5), starting from the dopamine D3 receptor sequence to screen a genomic DNA library. The MC5 comprises a sequence of 325 aminoacids, displaying 45-62% identity with other melanocortin receptors and 82% identity with its human counterpart that we cloned thereafter. The sequence of the latter is identical to that of a so-called ′MC2′ receptor (Chhajlani et al., 1993, Biochem. Biophys. Res, Comm. 195, 866-873). The MC5, stably expressed in CHO cells, mediates increase in cAMP accumulation with a characteristic pharmacology: αMSH is twice as potent as NDPαMSH, 10 times as ACTH and 100 times as γMSH. Very low expression levels were detected in brain, while high levels were found in adrenals, stomach, lung and spleen. In addition, in situ hybridization studies show the MC5 expressed in the three layers of the adrenal cortex, predominantly in the aldosterone-producing zona glomerulosa cells.