Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat

Zhi-Hua Zhang; Robert B Felder

doi:10.1152/ajpregu.00504.2003

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Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat

Journal article

Peer reviewed

Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat

Zhi-Hua Zhang and Robert B Felder

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.286(2), pp.R303-310

02/2004

DOI: 10.1152/ajpregu.00504.2003

PMID: 14707012

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Abstract

The central pathways and mediators involved in sympathoexcitatory responses to circulating leptin are not well understood, although the arcuate-paraventricular nucleus (ARC-PVN) pathway likely plays a critical role. In urethane-anesthetized rats, ipsilateral intracarotid artery (ICA) injection of murine leptin (100 microg/kg) activated most PVN neurons tested. These responses were reduced by intracerebroventricular injection of the melanocortin subtype 3 and 4 receptor (MC3/4-R) antagonist SHU-9119 (0.6 nmol). The MC3/4-R agonist MTII (0.6 nmol icv) activated PVN neurons. Some PVN neurons that were excited by ICA leptin were inhibited by local application of neuropeptide Y (NPY, 2.5 ng). ICA leptin (100 microg/kg) excited presympathetic rostral ventrolateral medulla neurons and renal sympathetic nerve activity without significant change in blood pressure or heart rate; these effects were mimicked by intracerebroventricular injection of MTII (0.6 nmol). These data provide in vivo electrophysiological evidence to support the hypothesis that circulating leptin activates the sympathetic nervous system by stimulating the release of alpha-melanocyte-stimulating hormone in the vicinity of PVN neurons that are inhibited by the orexogenic peptide NPY.

Paraventricular Hypothalamic Nucleus - physiology

Receptor, Melanocortin, Type 4 - antagonists & inhibitors

Carotid Arteries

Medulla Oblongata - drug effects

Melanocyte-Stimulating Hormones - pharmacology

Rats

Male

Neuropeptide Y - pharmacology

Rats, Sprague-Dawley

Leptin - physiology

Paraventricular Hypothalamic Nucleus - cytology

Medulla Oblongata - cytology

Paraventricular Hypothalamic Nucleus - drug effects

Animals

Leptin - blood

Receptor, Melanocortin, Type 3 - antagonists & inhibitors

Neurons - physiology

Leptin - administration & dosage

Receptor, Melanocortin, Type 3 - physiology

Neurons - drug effects

Medulla Oblongata - physiology

Injections, Intra-Arterial

Receptor, Melanocortin, Type 4 - physiology

Details

Title: Subtitle: Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat
Creators: Zhi-Hua Zhang - Univ. of Iowa College of Medicine, E318-GH, 200 Hawkins Dr., Iowa City, IA 52242, USA. robert-felder@uiowa.edu
Robert B Felder
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.286(2), pp.R303-310
Publisher: United States
DOI: 10.1152/ajpregu.00504.2003
PMID: 14707012
ISSN: 0363-6119
eISSN: 1522-1490
Grant note: P01 HL-04388 / NHLBI NIH HHS
Language: English
Date published: 02/2004
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984065476802771

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