PAC1 receptor: emerging target for septic shock therapy.
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.
Martínez
Carmen
C
Department of Cell Biology, Faculty of Medicine, Complutense University, Ciudad Universitaria, 28040 Madrid, Spain. cmmora@bio.ucm.es
Arranz
Alicia
A
Juarranz
Yasmina
Y
Abad
Catalina
C
García-Gómez
María
M
Rosignoli
Florencia
F
Leceta
Javier
J
Gomariz
Rosa P
RP
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
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide