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.

• Authors: Carmen Martínez, Alicia Arranz, Yasmina Juarranz, Catalina Abad, María García-Gómez, Florencia Rosignoli, Javier Leceta, Rosa P Gomariz
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1070 Pg. 405-10 (Jul 2006) ISSN: 0077-8923 [Print] United States
• PMID: 16888200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pituitary Adenylate Cyclase-Activating Polypeptide
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
• Vasoactive Intestinal Peptide

Topics

• Animals
• Mice
• Mice, Knockout
• Pituitary Adenylate Cyclase-Activating Polypeptide (therapeutic use)
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I (deficiency, genetics, metabolism)
• Shock, Septic (drug therapy, genetics, metabolism)
• Survival Rate
• Vasoactive Intestinal Peptide (therapeutic use)