Melanocortin 4 receptors in the paraventricular nucleus modulate the adipose afferent reflex in rat
Open accessAbstract
BACKGROUND AND AIM: Paraventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats. METHODOLOGY/PRINCIPAL FINDINGS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. AAR was evaluated using RSNA and MAP responses to capsaicin injection into the inguinal white adipose tissue (iWAT). Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR. The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response. The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN. Furthermore, both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN. SHU9119 in the PVN abolished the increase in cAMP level which induced by iWAT injection of capsaicin. CONCLUSION: The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.
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The MC4R is a G protein-coupled 7 transmembrane receptor that increases cAMP phosphorylation and activates protein kinase A.
“The MC4R is a G protein-coupled 7 transmembrane receptor that increases cAMP phosphorylation and activates protein kinase A (PKA) [3, 26, 63]; therefore, blockade of these intracellular pathways attenuates MC4R actions [3, 63].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [63]
Blockade of intracellular pathways downstream of MC4R attenuates MC4R actions.
“The MC4R is a G protein-coupled 7 transmembrane receptor that increases cAMP phosphorylation and activates protein kinase A (PKA) [3, 26, 63]; therefore, blockade of these intracellular pathways attenuates MC4R actions [3, 63].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [63]
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- Authors
- Li, P., Sun, H.-J., Zhang, L.-L., Ding, L., Han, Y., Zhu, G.-Q., & Zhou, Y.-B.
- Affiliations
- Jiangsu Province Hospital (CN)
- Nanjing Medical University (CN)
- Corresponding author
- Zhou, Ye-Bo
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-11-11
- Volume
- 8
- Issue
- 11
- Pages
- e80295
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3823614
- OpenAlex
- W1973804671
- Cited by
- 17
- References
- 33
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 1
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31171095, 81000106, 31271213)
- Nanjing Medical University
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- melanocortin-4 receptor, melanocortin 3 receptor, paraventricular nucleus, melanotan II, SHU9119, cAMP/PKA signaling, renal sympathetic nerve activity, capsaicin, white adipose tissue, hypothalamus, blood pressure
- MeSH terms
- Adenylyl Cyclase Inhibitors, Adenylyl Cyclases, Adipose Tissue, Animals, Male, Melanocyte-Stimulating Hormones, Paraventricular Hypothalamic Nucleus, Peptides, Cyclic, Reflex, Rats, Sprague-Dawley, Receptor, Melanocortin, Type 4, Rats
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