The natriuretic mechanism of Gamma-Melanocyte-Stimulating Hormone.

Gamma-Melanocyte Stimulating Hormone (Gamma-MSH) regulates sodium (Na(+)) balance and blood pressure through activation of the melanocortin receptor 3 (MC3-R). The mechanism of the natriuretic effect is proposed to involve binding of MC3-R either in the kidney to directly inhibit tubular Na(+) transport or in the brain to inhibit central neural pathways that control renal tubular Na(+) absorption. This study aimed to clarify the mechanism involved in the natriuretic effect of Gamma-MSH on MC3-R in kidney cells. In Ussing chamber studies, we observed no effects of Gamma-MSH on NaCl transport in the mouse inner medullary collecting duct cell line (mIMCD-K2). We also found that neither MC3-R protein nor mRNA was expressed in mouse kidney, suggesting that renal Gamma-MSH action may not be mediated through direct effects on tubular Na(+) transport but rather through effects on central neural pathways that innervate the kidney.