INVESTIGADORES
VATTA Marcelo Sergio
congresos y reuniones científicas
Título:
ROLE OF ATRIAL NATRIURETIC FACTOR (ANF) AND MRP4 IN THE ONSET OF ACUTE PANCREATITIS IN THE RAT
Autor/es:
VENTIMIGLIA M; NAJENSON AC; PERAZZO JC; CAROZZIO A; VATTA MS; DAVIO CA; BIANCIOTTI LG
Lugar:
IGUASSU FALLS
Reunión:
Congreso; 1ST PANAMERICAN CONGRESS OF PHYSIOLOGICAL SCIENCES; 2014
Institución organizadora:
ALACF-APS-IUPS
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 secretinevoked
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.