Premium
[Nle 3 , d ‐Phe 6 ]‐γ 2 ‐melanocyte‐stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ 2 ‐melanocyte‐stimulating hormone in anaesthetized rats
Author(s) -
Cope Georgina,
Flanagan Evelyn T,
Houghton Belinda L,
Walsh Sarah A,
Johns Edward J,
Healy Vincent
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12025
Subject(s) - endocrinology , medicine , melanocyte stimulating hormone , chemistry , excretion , kidney , receptor , natriuresis , sodium , hormone , excretory system , renal function , diuretic , biology , organic chemistry
Summary The present study compared the cardiovascular and renal actions of γ 2 ‐melanocyte‐stimulating hormone (γ 2 MSH ) with those of the synthetic analogue [Nle 3 , d ‐Phe 6 ]‐γ 2 MSH ( NDP ‐γ 2 MSH ) and explored the effects of high dietary salt intake on the renal actions of NDP ‐γ 2 MSH . Both peptides were infused systemically (3–1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated rats fed either a normal (0.4% NaCl) or high‐salt (4% NaCl; HS ) diet. Mean arterial pressure ( MAP ), glomerular filtration rate ( GFR ), urinary sodium excretion ( U N a V), urinary output ( UV ) and fractional sodium excretion were determined, as was expression of the melanocortin MC 3 receptor in inner medullary collecting duct ( IMCD ) epithelial cells. Both renal and systemic infusion of γ 2 MSH increased MAP by 23 ± 2% and 54 ± 4%, respectively, but equivalent doses of NDP ‐γ 2 MSH had no significant pressor effects. Both peptides had similar natriuretic and diuretic effects in rats fed a normal salt diet. However, NDP ‐γ 2 MSH increased U N a V and UV by two‐ to threefold in rats fed the normal salt diet and by six‐ to sevenfold in rats fed the HS diet. Furthermore, NDP ‐γ 2 MSH induced a 3.5‐fold increase in GFR only in rats fed the HS diet. These renal effects of NDP ‐γ 2 MSH were not abolished by prior renal denervation. Rats fed the HS diet also exhibited a 4.5‐fold increase in MC 3 receptor expression in IMCD epithelial cells. Intrarenal infusion of NDP ‐γ 2 MSH induced the natriuretic but not the cardiovascular effects exhibited by γ 2 MSH . The renal activities may be attributed to a direct binding of NDP ‐γ 2 MSH to MC 3 receptors expressed in IMCD cells, leading to a potent natriuretic effect that is independent of renal innervation.