The natriuretic mechanism of Gamma-Melanocyte-Stimulating Hormone

Abstract

γ-Melanocyte Stimulating Hormone (γ-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 γ-MSH on MC3-R in kidney cells. In Ussing chamber studies, we observed no effects of γ-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 γ-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.

Both MC 1 and MC 3 Receptors Provide Protection From Cerebral Ischemia-Reperfusion–Induced Neutrophil Recruitment

“…However initial analysis of MC 1 and MC 3 protein expression using western blotting revealed antibody binding in MC 3 -/- mice, using both the Sigma Aldrich (M4937) and Acris (AP10124PU-N) MC 3 antibodies, despite PCR confirmation of the MC 3 -/- (Supplemental figure V). This suggests that both antibodies tested display non-specific binding to protein at a similar molecular weight to MC 3 , as has been previously described 10 . Therefore, qRT-PCR was used to quantify MC expression at the mRNA level.…”

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016

“…In another report, icv administration of γ 2 -MSH in rats fasted for 24 h yielded no effect on food intake [78], confounding the role γ-MSH peptides may play in regulating food intake. Additional studies of γ-MSH ligands have examined the role of this ligand on cardiovascular, sodium, and blood pressure regulation [79-81]. …”

C‐terminal tails mimicking bioactive intermediates cause different plasma degradation patterns and kinetics in neuropeptides γ‐MSH, α‐MSH, and neurotensin

“…For example, Sacubitrilat is a Food and Drug Administration (FDA)–approved inhibitor of NEP used to treat heart failure via blocking vasodilatation 29 . Given the role of γ‐MSHs in natriuresis 30 and therefore vasodilatation, and the presence of a “NEP cleavage signature” upon plasma incubation, we investigated whether this endo‐protease is involved in γ2‐MSH* degradation. To this aim, we used the commercially available phosphoramidon inhibitor 24 .…”