HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/G349    most recent 00163.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Sabbatini, M. E. Articles by Bianciotti, L. G. Search for Related Content PubMed PubMed Citation Articles by Sabbatini, M. E. Articles by Bianciotti, L. G.

HORMONES AND SIGNALING

Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas

¹Cátedras de Fisiopatología, ²Fisiología-IQUIMEFA-CONICET, and ³Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

Submitted 17 April 2006 ; accepted in final form 6 September 2006

We previously reported that atrial natriuretic factor (ANF) stimulates pancreatic secretion through NPR-C receptors coupled to PLC and potentiates secretin response without affecting cAMP levels. In the present study we sought to establish the intracellular signaling mechanism underlying the interaction between both peptides. In isolated pancreatic acini 100 nM ANF abolished cAMP accumulation evoked by any dose of secretin. Lower doses of ANF (1 fM, 1 pM, 1 and 10 nM) dose dependently reduced EC₅₀ secretin-evoked cAMP. Although ANF failed to affect cAMP stimulated by amthamine (selective H2 agonist) or isoproterenol (-adrenergic agonist), it abolished VIP-induced cAMP formation. ANF inhibitory effect was prevented by U-73122 (PLC inhibitor) and GF-109203X (PKC inhibitor) but unaltered by PKG and nitric oxide synthase inhibition, supporting that the PLC/PKC pathway mediated the effect. ANF response was mimicked by cANP (4–23 amide) and abolished by pertussis toxin, strongly supporting NPR-C receptor activation. In vivo studies showed that ANF at 0.5 µg·kg^–1·h^–1 enhanced secretion stimulated by 1 U·kg^–1·h^–1 secretin but at 1 and 2 µg·kg^–1·h^–1 it abolished secretin response. However, ANF at such doses failed to modify the secretion evoked by carbachol or CCK. Present results show that ANF negatively modulated secretin secretory response and intracellular signaling through the activation of NPR-C receptors coupled to the PLC/PKC pathway. Furthermore, the finding that ANF also inhibited VIP-evoked cAMP supports a selective modulation of class II G-protein coupled receptors by ANF. Present findings suggest that ANF may play a protective role by reducing secretin response to avoid overstimulation.

adenosine 3',5'-cyclic monophosphate; pancreatic flow; phospholipase C; protein kinase C

This article has been cited by other articles:

				M. E. Sabbatini, M. Rodriguez, M. B. di Carlo, C. A. Davio, M. S. Vatta, and L. G. Bianciotti C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G987 - G994. [Abstract] [Full Text] [PDF]