Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin

Kamal Rahmouni; William G Haynes; Donald A Morgan; Allyn L Mark

doi:10.1523/JNEUROSCI.23-14-05998.2003

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Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin

Journal article

Open access

Peer reviewed

Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin

Kamal Rahmouni, William G Haynes, Donald A Morgan and Allyn L Mark

The Journal of neuroscience, Vol.23(14), pp.5998-6004

07/09/2003

DOI: 10.1523/JNEUROSCI.23-14-05998.2003

PMCID: PMC6740337

PMID: 12853417

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Abstract

Central melanocortin signaling plays an important role in regulation of energy homeostasis by leptin and insulin. We investigated the interaction between leptin, insulin, and melanocortin-4 receptors (MC-4Rs) in the control of renal sympathetic nerve activity (RSNA) in mice. We compared the effects of intracerebroventricular (ICV) administration of leptin, insulin, MC-3/4R agonist (MTII), and corticotrophin-releasing factor (CRF) on RSNA in leptin receptor-deficient (db/db) mice, MC-4R knock-out mice, and their wild-type controls. ICV administration of leptin and MTII caused a significant and dose-dependent increase in RSNA in control mice. As expected, leptin had no significant effect on RSNA in the db/db mice. Interestingly, db/db mice exhibited markedly attenuated RSNA responses to ICV administration of MTII. However, the increase in RSNA induced by insulin and CRF was comparable between db/db and control mice. In the heterozygous and homozygous MC-4R knock-out mice, the RSNA response to MTII was attenuated and abolished, respectively. The RSNA response to ICV leptin and insulin was also attenuated and abolished in the heterozygous and homozygous MC-4R knock-out mice, respectively. In contrast, CRF induced a similar increase in RSNA in the MC-4R knock-out and wild-type mice. Our data demonstrate that in the absence of leptin receptors, the sympathoexcitatory effects of melanocortin system stimulation are attenuated. In addition, the renal sympathoexcitatory responses to leptin and insulin are dependent on the MC-4R, demonstrating an important role for the MC-4R in the regulation of renal sympathetic nerve outflow by leptin and insulin.

Kidney - physiology

alpha-MSH - pharmacology

Insulin - physiology

Sympathetic Nervous System - drug effects

Injections, Intraventricular

Body Weight - drug effects

Hemodynamics - physiology

Insulin - blood

Leptin - physiology

Receptor, Melanocortin, Type 4

Leptin - blood

Sympathetic Nervous System - physiology

Leptin - administration & dosage

Corticotropin-Releasing Hormone - administration & dosage

Action Potentials - drug effects

Receptors, Leptin

Receptors, Corticotropin - physiology

Mice, Inbred C57BL

Insulin - administration & dosage

Receptors, Corticotropin - agonists

Mice, Knockout

Action Potentials - physiology

Corticotropin-Releasing Hormone - physiology

Animals

Receptors, Cell Surface - deficiency

Kidney - innervation

Hemodynamics - drug effects

Mice

Receptors, Corticotropin - genetics

Body Weight - physiology

alpha-MSH - analogs & derivatives

Receptors, Cell Surface - genetics

Details

Title: Subtitle: Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin
Creators: Kamal Rahmouni - Hypertension Genetics Specialized Center of Research, and Department of Internal Medicine, University of Iowa and the Veterans Administration Medical Center, Iowa City, Iowa 52242, USA. kamal-rahmouni@uiowa.edu
William G Haynes
Donald A Morgan
Allyn L Mark
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.23(14), pp.5998-6004
Publisher: United States
DOI: 10.1523/JNEUROSCI.23-14-05998.2003
PMID: 12853417
PMCID: PMC6740337
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: HL 14388 / NHLBI NIH HHS HL 44546 / NHLBI NIH HHS
Language: English
Date published: 07/09/2003
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040570502771

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