C-type natriuretic peptide stimulates pancreatic exocrine secretion in the rat: role of vagal afferent and efferent pathways.
We previously reported that C-type natriuretic peptide (CNP) increases amylase release in isolated pancreatic acini through natriuretic peptide receptor C activation and enhances pancreatic exocrine secretion via vagal pathways when applied to the brain. In the present study we sought to establish whether CNP was involved in the peripheral regulation of pancreatic secretion. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation and bile diversion into the duodenum. CNP dose-dependently enhanced pancreatic flow, chloride and protein excretion but did not modify bicarbonate output. A selective natriuretic peptide receptor C agonist enhanced pancreatic flow and mimicked CNP-evoked protein output but failed to modify chloride secretion. Truncal vagotomy, perivagal application of capsaicin and hexamethonium reduced CNP-evoked pancreatic flow and abolished chloride excretion but did not affect protein output. Furthermore, pre-treatment with atropine reduced both CNP-stimulated pancreatic flow and chloride excretion but failed to modify protein excretion. Partial muscarinic blockade of CNP-evoked chloride output suggested that mediators other than acetylcholine were involved. However, CNP response was unaltered by cholecystokinin and vasoactive intestinal peptide receptor blockade or by nitric oxide synthase inhibition. In conclusion, CNP-stimulated pancreatic flow through the activation of the natriuretic peptide receptor C and the vago-vagal reflex but it increased protein output only by natriuretic peptide receptor C activation and chloride excretion by vago-vagal reflexes. Present results suggest that CNP may play a role as a local regulator of the exocrine pancreas.
Sabbatini
María E
ME
Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Rodríguez
Myrian R
MR
Dabas
Paula
P
Vatta
Marcelo S
MS
Bianciotti
Liliana G
LG
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001639:Bicarbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D002766:Cholecystokinin / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000819:agonists; D013268:Stimulation, Chemical; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D001639:Bicarbonates; D002712:Chlorides; D020098:Natriuretic Peptide, C-Type; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D002766:Cholecystokinin; D017461:Receptors, Atrial Natriuretic Factor