INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Role of atrial natriuretic factor and MRP4 in the onset of acute pancreatitis in the rat.
Autor/es:
MARIA S. VENTIMIGLIA; ANA CLARA NAJENSON; JUAN C. PERAZZO; ALEJANDRO CAROZZO; MARCELO S. VATTA; LILIANA G. BIANCIOTTI
Lugar:
Foz de Iguazu
Reunión:
Congreso; First Panamerican Congress of Physiological Sciences.; 2014
Resumen:
We previously reported that ANF extrudes secretin-evoked cAMP in the exocrine pancreas through MRP4. Given that increased cAMP sensitizes zymogen granules predisposing to the development of acute pancreatitis (AP) we aimed to evaluate whether ANF by extruding cAMP through MRP4 played any role in the onset of the disease. AP was by repetitive caerulein injections induced in Sprague Dawley rats pretreated with or without probenecid (general MRPs inhibitor) and infused with secretin alone or with ANF. Plasma amylase and intrapancreatic trypsin were measured and histological examination of the pancreas performed. Blockade of MRP4 in secretin treated rats not only increased trypsin but it also induced the appearance of cytoplasmic vacuoles, a hallmark of AP. Such alterations were prevented by ANF. MRPs blockade in rats with AP enhanced trypsinogen activation and larger cytoplasmic vacuoles as well as larger areas of necrosis and edema further aggravated by secretin but not prevented by ANF. The temporal resolution of intracellular cAMP levels appears to be critical in the onset of AP given that secretin-evoked cAMP in a context of MRPs inhibition makes the pancreas prone to injury in normal rats and further it aggravates the onset of AP. Present findings support a protective role for ANF in acinar cells by extruding cAMP through MRP4 and further suggest that the regulation of MRP4 by ANF would play a relevant role in maintaining pancreatic acinar cell homeostasis.