Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney
Abstract
Gamma-melanocyte stimulating hormone (gamma-MSH) is a circulating natriuretic peptide hormone derived from proopiomelanocortin (POMC); its concentration in plasma and pituitary POMC mRNA abundance, increase in rats ingesting a high-sodium diet (HSD, 8% NaCl) compared with a low-sodium diet (LSD, 0.07% NaCl). RT-PCR of rat kidney RNA demonstrated reaction products of the expected size in both cortex and medulla for MC3-R, MC4-R, and MC5-R mRNA; no signal for MC1-R or MC2-R was detected. Relative to beta-actin or cyclophilin, abundance of the three receptor transcripts after 1 wk of the LSD was approximately equal in both cortex and medulla. After 1 wk of the HSD, mRNA abundance of MC4-R and MC5-R was unchanged, whereas that of MC3-R in medulla more than doubled, the ratio of MC3-R/beta-actin signal increasing from 0.38 +/- 0.04 on LSD to 0.84 +/- 0.04 on HSD (P < 0.001). No significant increase occurred in the cortex. The increase in MC3-R expression induced by dietary sodium was observed in inner medullary collecting duct (IMCD) cells isolated from the kidneys of HSD rats, suggesting that these cells were the major site of receptor expression in the medulla. Immunoblots of whole medullary and IMCD cell homogenates detected MC3-R immunoreactive protein; its expression was twice as great in samples from HSD vs. LSD rat kidneys, paralleling the increase in MC3-R mRNA abundance on the HSD. No changes in MC4-R or MC5-R protein expression were observed. Incubation of IMCD cell suspensions with increasing concentrations of gamma2-MSH led to increased cAMP accumulation, with values from rats on the HSD being roughly double the values from LSD rats. Intrarenal infusion of gamma2-MSH (500 fmol/min) increased sodium and cAMP excretion from the infused but not contralateral kidney of HSD rats, while having no effect in LSD rats. These data show that MC3-R is expressed in rat IMCD cells in a manner modulated by dietary sodium intake. Because MC3-R is the receptor with which gamma-MSH interacts, our findings suggest the existence of a sodium-regulating system, activated in response to a HSD, which increases urinary sodium excretion to balance the high-sodium intake.
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High salt intake increases MC3R mRNA and protein in inner medullary collecting duct cells.
“High salt intake increases MC3R mRNA and protein in inner medullary collecting duct cells suggesting that γ-MSH–MC3R activation may contribute to natriuresis during increased sodium intake [21].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [21]
γ-MSH-MC3R activation may contribute to natriuresis during increased sodium intake.
“High salt intake increases MC3R mRNA and protein in inner medullary collecting duct cells suggesting that γ-MSH–MC3R activation may contribute to natriuresis during increased sodium intake [21].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [21]
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- Authors
- Ni, X.-P., Bhargava, A., Pearce, D., & Humphreys, M. H.
- Affiliations
- San Francisco General Hospital (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2006-03
- Volume
- 290
- Issue
- 3
- Pages
- R560-R567
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2110190860
- Cited by
- 34
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2022: 2 · 2021: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R-O1-HL-68871, R01HL068871)
- National Institute of Diabetes and Digestive and Kidney Diseases (R-O1-DK-51151, R-O1-DK-56695, R01DK056695)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Keywords
- melanocortin 3 receptor, sodium intake, high-salt diet, gamma-MSH, sodium excretion, inner medullary collecting duct, renal medulla, cAMP signaling, proopiomelanocortin, melanocortin receptors, renal sodium excretion, gene expression regulation, rat kidney, intrarenal infusion
- MeSH terms
- Adaptation, Physiological, Animals, Eating, Kidney, Male, RNA, Messenger, Sodium, Dietary, Water-Electrolyte Balance, Rats, Sprague-Dawley, gamma-MSH, Receptor, Melanocortin, Type 3, Rats
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