HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/E1697    most recent 00098.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, R. Articles by Wang, P. Search for Related Content PubMed PubMed Citation Articles by Wu, R. Articles by Wang, P.

Ghrelin inhibits sympathetic nervous activity in sepsis

Center for Immunology and Inflammation, The Feinstein Institute for Medical Research and Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, New York

Submitted 13 February 2007 ; accepted in final form 24 September 2007

Our previous studies have shown that norepinephrine (NE) upregulates proinflammatory cytokines by activating ₂-adrenoceptor. Therefore, modulation of the sympathetic nervous system represents a novel treatment for sepsis. We have also shown that a novel stomach-derived peptide, ghrelin, is downregulated in sepsis and that its intravenous administration decreases proinflammatory cytokines and mitigates organ injury. However, it remains unknown whether ghrelin inhibits sympathetic activity through central ghrelin receptors [i.e., growth hormone secretagogue receptor 1a (GHSR-la)] in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). Ghrelin was administered through intravenous or intracerebroventricular injection 30 min before CLP. Our results showed that intravenous administration of ghrelin significantly reduced the elevated NE and TNF- levels at 2 h after CLP. NE administration partially blocked the inhibitory effect of ghrelin on TNF- in sepsis. GHSR-la inhibition by the administration of a GHSR-la antagonist, [D-Arg¹,D-Phe⁵, D-Trp^7,9,Leu¹¹]substance P, significantly increased both NE and TNF- levels even in normal animals. Markedly elevated circulating levels of NE 2 h after CLP were also significantly decreased by intracerebroventricular administration of ghrelin. Ghrelin's inhibitory effect on NE release was completely blocked by intracerebroventricular injection of the GHSR-1a antagonist or a neuropeptide Y (NPY)/Y₁ receptor antagonist. However, ghrelin's downregulatory effect on TNF- release was only partially diminished by these agents. Thus ghrelin has sympathoinhibitory properties that are mediated by central ghrelin receptors involving a NPY/Y1 receptor-dependent pathway. Ghrelin's inhibitory effect on TNF- production in sepsis is partially because of its modulation of the overstimulated sympathetic nerve activation.

ghrelin; sepsis; sympathetic nervous system; norepinephrine; cytokines

This article has been cited by other articles:

				F. Sayk, A. Vietheer, B. Schaaf, P. Wellhoener, G. Weitz, H. Lehnert, and C. Dodt Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R891 - R898. [Abstract] [Full Text] [PDF]