The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones
Abstract
OBJECTIVE: Alpha and gamma-melanocyte stimulating hormones (MSH) are peptides that possess potent hypertensinogenic actions when injected intravenously or intracerebroventricularly. We sought to define the central receptor(s) mediating these cardiovascular actions. METHODS: We gave bolus injections of synthetic alpha or gamma-MSH intravenously or intracerebroventricularly to anesthetized wild-type (Mc3r+/+, Mc4r+/+) mice and mice with targeted disruption of the gamma-MSH receptor (Mc3r-/-) or the melanocortin 4 receptor (Mc4r-/-). RESULTS: Gamma-MSH injected intravenously increased mean arterial pressure (MAP) and heart rate (HR) dose-dependently, with the effect being evident at 10 mol/kg; the maximum increase, at 10 mol/kg, was 38 mmHg in both strains from similar control MAP. Parallel increases in HR also occurred. Injection of the sodium channel blocker, benzamil, 4 microg/kg intracerebroventricularly, before intravenous gamma-MSH completely prevented the increases in MAP and HR in both strains. Injection of 2 x 10 mol/g body weight alpha-MSH intravenously had no effect on MAP or HR in Mc4r wild-type or -/- mice. However, the same dose given intracerebroventricularly to wild-type mice increased MAP from 76 +/- 4 to 95 +/- 5 mmHg at 10 min (P < 0.01) and HR from 416 +/- 15 to 480 +/- 15 beats/min (P < 0.01). In Mc4r-/- mice, the intracerebroventricular administration of the peptide did not alter these variables, in contrast to the results in wild-type mice. CONCLUSION: Both MSH peptides exert their hypertensinogenic effects through central sites of action, which probably reflect the activation of sympathetic outflow. The actions of intracerebroventricular alpha-MSH appear to be mediated via Mc4r, whereas those of gamma-MSH are independent of its receptor Mc3r, but reflect the activation of a sodium channel in the central nervous system. These results help to reconcile the hypertensive action of gamma-MSH injections with the hypertension observed in states of gamma-MSH deficiency.
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The effects of γ-MSH on blood pressure in wild-type mice were completely abolished by benzamil injected into the lateral ventricle.
“However, the effects of γ-MSH on BP in WT mice were completety abolished by benzamil, an amiloride analog, injected into the lateral ventricle [19].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [19]
γ-MSH interacts with Phe-Met-Arg-Phe-NH2 gated sodium channels to induce sympathetic nervous system activation and increased blood pressure.
“These findings suggest that γ-MSH interacts with Phe-Met-Arg-Phe-NH2 (FMRFamide) gated sodium channels to induce SNS activation and increased BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [19]
Acute intracerebroventricular injections of α-MSH increase sympathetic nervous system activity and blood pressure.
“Several previous studies have shown that acute ICV injections of α-MSH increase SNS activity and BP [19, 23, 24].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [19]
The blood pressure effects of α-MSH require activation of central nervous system MC4R since blood pressure responses to α-MSH administered directly into the central nervous system were completely abolished in MC4R deficient mice.
“The BP effects of α-MSH also require activation of CNS MC4R since BP responses to α-MSH administered directly into the CNS were completety abolished in MC4R deficent mice [19].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [19]
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Metadata
- Authors
- Ni, X.-P., Butler, A. A., Cone, R. D., & Humphreys, M. H.
- Affiliations
- San Francisco General Hospital (US)
- Pennington Biomedical Research Center (US)
- National Institutes of Health (US)
- Corresponding author
- Humphreys, Michael H
- Venue
- Journal of Hypertension
- Published
- 2006-11
- Volume
- 24
- Issue
- 11
- Pages
- 2239-2246
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W2015747167
- Cited by
- 88
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 8 · 2018: 2 · 2017: 6 · 2016: 9 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 7
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01-HL-68871, R01HL068871)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK051730, DK51730, R01-DK55819)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- melanocyte-stimulating hormone, alpha-melanocyte-stimulating hormone, gamma-MSH, melanocortin-4 receptor, melanocortin 3 receptor, central hypertension, sodium channels, benzamil, sympathetic nervous system, heart rate, mean arterial pressure, intracerebroventricular administration, knockout mice
- MeSH terms
- alpha-MSH, Amiloride, Animals, Blood Pressure, Dose-Response Relationship, Drug, Heart Rate, Hypertension, Sympatholytics, Mice, Knockout, gamma-MSH, Models, Animal, Sodium Channel Blockers, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Mice
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