title: 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.
authors.affiliation: Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956-Piso 5, 1113 Buenos Aires, Argentina.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Sabbatini
authors.forename: Alberto
authors.initials: A
authors.lastname: Villagra
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Davio
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Vatta
authors.forename: Belisario E
authors.initials: BE
authors.lastname: Fernandez
authors.forename: Liliana G
authors.initials: LG
authors.lastname: Bianciotti
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002766:Cholecystokinin / Q000502:physiology; D004573:Electrolytes / Q000378:metabolism; D006162:Guanylate Cyclase / Q000502:physiology*; D006868:Hydrolysis / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology*; D012633:Secretin / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D004573:Electrolytes; D010716:Phosphatidylinositols; D011506:Proteins; D012633:Secretin; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D002766:Cholecystokinin; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C