Atrial natriuretic factor stimulates exocrine pancreatic secretion in the rat through NPR-C receptors

Abstract

Increasing evidence supports the role of atrial natriuretic factor (ANF) in the modulation of gastrointestinal physiology. The effect of ANF on exocrine pancreatic secretion and the possible receptors and pathways involved were studied in vivo. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation, and bile diversion into the duodenum. ANF dose-dependently increased pancreatic secretion of fluid and proteins and enhanced secretin and CCK-evoked response. ANF decreased chloride secretion and increased the pH of the pancreatic juice. Neither cholinergic nor adrenergic blockade affected ANF-stimulated pancreatic secretion. Furthermore, ANF response was not mediated by the release of nitric oxide. ANF-evoked protein secretion was not inhibited by truncal vagotomy, atropine, or Nomega-nitro-l-arginine methyl ester administration. The selective natriuretic peptide receptor-C (NPR-C) receptor agonist cANP-(4-23) mimicked ANF response in a dose-dependent fashion. When the intracellular signaling coupled to NPR-C receptors was investigated in isolated pancreatic acini, results showed that ANF did not modify basal or forskolin-evoked cAMP formation, but it dose-dependently enhanced phosphoinositide hydrolysis, which was blocked by the selective PLC inhibitor U-73122. ANF stimulated exocrine pancreatic secretion in the rat, and its effect was not mediated by nitric oxide or parasympathetic or sympathetic activity. Furthermore, CCK and secretin appear not to be involved in ANF response. Present findings support that ANF exerts a stimulatory effect on pancreatic exocrine secretion mediated by NPR-C receptors coupled to the phosphoinositide pathway.

Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation

“…To examine whether NPR-C mediates pump stimulation, we used two highly selective NPR-C ligands, AP-811 and ANP (4 -23). ANP(4 -23) can elicit a cellular response and is hence regarded as an NPR-C agonist (34). While AP-811 is a highly selective NPR-C ligand (19,38), it is not known whether it is an agonist or an antagonist.…”

Blockade of Multidrug Resistance-Associated Proteins Aggravates Acute Pancreatitis and Blunts Atrial Natriuretic Factor’s Beneficial Effect in Rats: Role of MRP4 (ABCC4)

“…María Silvia Ventimiglia, 1 Ana Clara Najenson, 1 Juan Carlos Perazzo, 1 Alejandro Carozzo, 3 Marcelo S Vatta, 2 Carlos A Davio, 3 and Liliana G Bianciotti We previously reported that atrial natriuretic factor (ANF) stimulates secretin-evoked cAMP efflux through multidrug resistanceassociated 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.…”

“…For this purpose, animals were infused with saline (control), secretin (1 U/kg/h) or ANF (1 μg/kg/h) alone or combined for 60 min. The doses of secretin and ANF were obtained from previous doseresponse curves (3). In another group of rats, acute pancreatitis was induced by four repetitive intraperitoneal injections of 40 μg/kg cerulein at hourly intervals and secretin infusion alone, or with ANF for 60 min starting 30 min before the first cerulein injection.…”

“…Results were expressed as picomoles per milliliter plasma. Determination of cAMP in pancreatic acini was expressed as percentage of control and performed as in previous studies (3,5,6).…”

“…Atrial natriuretic factor (ANF) is a key regulator of cardiovascular and renal function, but compelling evidence supports its physiological role in the digestive system where it modulates digestive motility and secretions in a paracrine and/or autocrine manner (1)(2)(3)(4). We previously reported that ANF through natriuretic peptide receptor type C (NPR-C) receptors coupled to phospholipase C/ protein kinase C (PLC/PKC) negatively modulates secretin intracellular signaling by stimulating secretin-evoked cAMP out of the pancreatic acinar cells through multidrug resistance-associated protein 4 (MRP4) (5,6).…”