PAC1 receptor: emerging target for septic shock therapy.

Abstract:

:Septic shock is a systemic response to severe bacterial infections, generally caused by Gram-negative bacterial endotoxins, with multiple manifestations such as hypotension, tissue injury, disseminated intravascular coagulation, and multi-organ failure. All these effects, are induced by the generation of pro-inflammatory and vasodilator mediators, cell adhesion molecules, coagulation factors, and acute-phase proteins. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two immunopeptides with anti-inflammatory properties exerted through type 1 and 2 VIP receptors (VPAC1 and VPAC2, respectively), and PACAP receptor (PAC1). The present results recapitulate the protective role of PAC1 in an experimental model of lethal endotoxemia using a knockout for the PAC1 receptor. Our results demonstrate that VIP and PACAP decrease lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) production, neutrophil infiltration and intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and fibrinogen expression through PAC1 receptor, providing an advantage to design more specific drugs complementing standard intensive care therapy in septic shock.

journal_name

Ann N Y Acad Sci

authors

Martínez C,Arranz A,Juarranz Y,Abad C,García-Gómez M,Rosignoli F,Leceta J,Gomariz RP

doi

10.1196/annals.1317.053

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

405-10

eissn

0077-8923

issn

1749-6632

pii

1070/1/405

journal_volume

1070

pub_type

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