title: 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.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Ciudad Universitaria, 28040 Madrid, Spain. cmmora@bio.ucm.es
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Alicia
authors.initials: A
authors.lastname: Arranz
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Juarranz
authors.forename: Catalina
authors.initials: C
authors.lastname: Abad
authors.forename: María
authors.initials: M
authors.lastname: García-Gómez
authors.forename: Florencia
authors.initials: F
authors.lastname: Rosignoli
authors.forename: Javier
authors.initials: J
authors.lastname: Leceta
authors.forename: Rosa P
authors.initials: RP
authors.lastname: Gomariz
mesh_terms: D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000627:therapeutic use; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012772:Shock, Septic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014660:Vasoactive Intestinal Peptide / Q000627:therapeutic use
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide