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Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2003 Jul 09; Vol. 23 (14), pp. 5998-6004. - Publication Year :
- 2003
-
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.
- Subjects :
- Action Potentials drug effects
Action Potentials physiology
Animals
Body Weight drug effects
Body Weight physiology
Corticotropin-Releasing Hormone administration & dosage
Corticotropin-Releasing Hormone physiology
Hemodynamics drug effects
Hemodynamics physiology
Injections, Intraventricular
Insulin administration & dosage
Insulin blood
Kidney innervation
Leptin administration & dosage
Leptin blood
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptor, Melanocortin, Type 4
Receptors, Cell Surface deficiency
Receptors, Cell Surface genetics
Receptors, Corticotropin agonists
Receptors, Corticotropin genetics
Receptors, Leptin
Sympathetic Nervous System drug effects
alpha-MSH pharmacology
Insulin physiology
Kidney physiology
Leptin physiology
Receptors, Corticotropin physiology
Sympathetic Nervous System physiology
alpha-MSH analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 23
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 12853417