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Artículo

Blockade of multidrug resistance associated proteins aggravates acute pancreatitis and blunts atrial natriuretic factor beneficial effect in rats: Role of MRP4/ABCC4

Ventimiglia, Maria SilviaIcon ; Najenson, Ana ClaraIcon ; Perazzo, Juan Carlos; Carozzo, Alejandro EnriqueIcon ; Vatta, Marcelo SergioIcon ; Davio, Carlos AlbertoIcon ; Bianciotti, Liliana GracielaIcon
Fecha de publicación: 05/2015
Editorial: Feinstein Inst Med Res
Revista: Molecular Medicine
ISSN: 1076-1551
e-ISSN: 1528-3658
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Patología

Resumen

We previously reported that atrial natriuretic factor (ANF) stimulates secretin-evoked cAMP efflux through multidrug resistance-associated protein 4 (MRP4) in the exocrine pancreas. Here we sought to establish in vivo whether this mechanism was involved in acute pancreatitis onset in the rat. Rats pretreated with or without probenecid (MRPs general inhibitor) were infused with secretin alone or with ANF. A set of these animals were given repetitive cerulein injections to induce acute pancreatitis. Plasma amylase and intrapancreatic trypsin activities were measured and histological examination of the pancreas performed. Secretin alone activated trypsinogen but induced no pancreatic histological changes. Blockade by probenecid in secretin-treated rats increased trypsin and also induced vacuolization, a hallmark of acute pancreatitis. ANF prevented the secretin response but in the absence of probenecid. In rats with acute pancreatitis, pretreatment with secretin aggravated the disease, but ANF prevented secretin-induced changes. Blockade of MRPs in rats with acute pancreatitis induced trypsinogen activation and larger cytoplasmic vacuoles as well as larger areas of necrosis and edema that were aggravated by secretin but not prevented by ANF. The temporal resolution of intracellular cAMP levels seems critical in the onset of acute pancreatitis, since secretin-evoked cAMP in a context of MRP inhibition makes the pancreas prone to injury in normal rats and aggravates the onset of acute pancreatitis. Present findings support a protective role for ANF mediated by cAMP extrusion through MRP4 and further suggest that the regulation of MRP4 by ANF would be relevant to maintain pancreatic acinar cell homeostasis.
Palabras clave: Mrps , Acute Pancreatitis , Secretin , Camp
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/13823
URL: http://molmed.org/journal/articles/43/1753
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461582/
URL: http://dx.doi.org/10.2119/molmed.2014.00166
Colecciones
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Ventimiglia, Maria Silvia; Najenson, Ana Clara; Perazzo, Juan Carlos; Carozzo, Alejandro Enrique; Vatta, Marcelo Sergio; et al.; Blockade of multidrug resistance associated proteins aggravates acute pancreatitis and blunts atrial natriuretic factor beneficial effect in rats: Role of MRP4/ABCC4; Feinstein Inst Med Res; Molecular Medicine; 21; 1; 5-2015; 58-67
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