C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas

Maria Eugenia Sabbatini, Myrian Rodríguez, María B. Di Carlo, Carlos A. Davio, Marcelo S. Vatta, Liliana G. Bianciotti

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Several studies show that C-type natriuretic peptide (CNP) has a modulatory role in the digestive system. CNP administration reduces both jejunal fluid and bile secretion in the rat. In the present study we evaluated the effect of CNP on amylase release in isolated pancreatic acini as well as the receptors and intracellular pathways involved. Results showed that all natriuretic peptide receptors were expressed not only in the whole pancreas but also in isolated pancreatic acini. CNP stimulated amylase secretion with a concentration- dependent biphasic response; maximum release was observed at 1 pM CNP, whereas higher concentrations gradually attenuated it. The response was mimicked by a selective natriuretic peptide receptor (NPR-C) agonist and inhibited by pertussis toxin, strongly supporting NPR-C receptor activation. CNP-evoked amylase release was abolished by U-73122 (PLC inhibitor) and 2-aminoethoxydiphenyl borate (2-APB) [an inositol 1,4,5-triphosphate (IP 3) receptor antagonist], partially inhibited by GF-109203X (PKC inhibitor), and unaltered by ryanodine or protein kinase A (PKA) and protein kinase G (PKG) inhibitors. Phosphoinositide hydrolysis was enhanced by CNP at all concentrations and abolished by U-73122. At 1 and 10 pM, CNP did not affect cAMP or guanosine 3′,5′-cyclic monophosphate (cGMP) levels, but at higher concentrations it increased cGMP and diminished cAMP content. Present findings show that CNP stimulated amylase release through the activation of NPR-C receptors coupled to the PLC pathway and downstream effectors involved in exocytosis. The attenuation of amylase release was likely related to cAMP reduction. The augmentation in cGMP supports activation of NPR-A/NPR-B receptors probably involved in calcium influx. Present findings give evidence that CNP is a potential direct regulator of pancreatic function.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume293
Issue number5
DOIs
StatePublished - Nov 1 2007

Fingerprint

C-Type Natriuretic Peptide
Exocrine Pancreas
Natriuretic Peptides
Peptide Receptors
Amylases
Fluids and Secretions
Cyclic GMP-Dependent Protein Kinases
Ryanodine
Digestive System
Inositol 1,4,5-Trisphosphate
Guanosine
Pertussis Toxin
Exocytosis
Protein Kinase Inhibitors
Phosphatidylinositols
Cyclic AMP-Dependent Protein Kinases
Bile
Pancreas
Hydrolysis

Keywords

  • Amylase secretion
  • Natriuretic peptide receptors
  • Phospholipase C
  • Protein kinase C

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas. / Sabbatini, Maria Eugenia; Rodríguez, Myrian; Di Carlo, María B.; Davio, Carlos A.; Vatta, Marcelo S.; Bianciotti, Liliana G.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 293, No. 5, 01.11.2007.

Research output: Contribution to journalArticle

Sabbatini, Maria Eugenia ; Rodríguez, Myrian ; Di Carlo, María B. ; Davio, Carlos A. ; Vatta, Marcelo S. ; Bianciotti, Liliana G. / C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2007 ; Vol. 293, No. 5.
@article{52d44af4ecc94489a77dc7674fa937ff,
title = "C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas",
abstract = "Several studies show that C-type natriuretic peptide (CNP) has a modulatory role in the digestive system. CNP administration reduces both jejunal fluid and bile secretion in the rat. In the present study we evaluated the effect of CNP on amylase release in isolated pancreatic acini as well as the receptors and intracellular pathways involved. Results showed that all natriuretic peptide receptors were expressed not only in the whole pancreas but also in isolated pancreatic acini. CNP stimulated amylase secretion with a concentration- dependent biphasic response; maximum release was observed at 1 pM CNP, whereas higher concentrations gradually attenuated it. The response was mimicked by a selective natriuretic peptide receptor (NPR-C) agonist and inhibited by pertussis toxin, strongly supporting NPR-C receptor activation. CNP-evoked amylase release was abolished by U-73122 (PLC inhibitor) and 2-aminoethoxydiphenyl borate (2-APB) [an inositol 1,4,5-triphosphate (IP 3) receptor antagonist], partially inhibited by GF-109203X (PKC inhibitor), and unaltered by ryanodine or protein kinase A (PKA) and protein kinase G (PKG) inhibitors. Phosphoinositide hydrolysis was enhanced by CNP at all concentrations and abolished by U-73122. At 1 and 10 pM, CNP did not affect cAMP or guanosine 3′,5′-cyclic monophosphate (cGMP) levels, but at higher concentrations it increased cGMP and diminished cAMP content. Present findings show that CNP stimulated amylase release through the activation of NPR-C receptors coupled to the PLC pathway and downstream effectors involved in exocytosis. The attenuation of amylase release was likely related to cAMP reduction. The augmentation in cGMP supports activation of NPR-A/NPR-B receptors probably involved in calcium influx. Present findings give evidence that CNP is a potential direct regulator of pancreatic function.",
keywords = "Amylase secretion, Natriuretic peptide receptors, Phospholipase C, Protein kinase C",
author = "Sabbatini, {Maria Eugenia} and Myrian Rodr{\'i}guez and {Di Carlo}, {Mar{\'i}a B.} and Davio, {Carlos A.} and Vatta, {Marcelo S.} and Bianciotti, {Liliana G.}",
year = "2007",
month = "11",
day = "1",
doi = "10.1152/ajpgi.00268.2007",
language = "English (US)",
volume = "293",
journal = "American journal of physiology. Gastrointestinal and liver physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - C-type natriuretic peptide enhances amylase release through NPR-C receptors in the exocrine pancreas

AU - Sabbatini, Maria Eugenia

AU - Rodríguez, Myrian

AU - Di Carlo, María B.

AU - Davio, Carlos A.

AU - Vatta, Marcelo S.

AU - Bianciotti, Liliana G.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Several studies show that C-type natriuretic peptide (CNP) has a modulatory role in the digestive system. CNP administration reduces both jejunal fluid and bile secretion in the rat. In the present study we evaluated the effect of CNP on amylase release in isolated pancreatic acini as well as the receptors and intracellular pathways involved. Results showed that all natriuretic peptide receptors were expressed not only in the whole pancreas but also in isolated pancreatic acini. CNP stimulated amylase secretion with a concentration- dependent biphasic response; maximum release was observed at 1 pM CNP, whereas higher concentrations gradually attenuated it. The response was mimicked by a selective natriuretic peptide receptor (NPR-C) agonist and inhibited by pertussis toxin, strongly supporting NPR-C receptor activation. CNP-evoked amylase release was abolished by U-73122 (PLC inhibitor) and 2-aminoethoxydiphenyl borate (2-APB) [an inositol 1,4,5-triphosphate (IP 3) receptor antagonist], partially inhibited by GF-109203X (PKC inhibitor), and unaltered by ryanodine or protein kinase A (PKA) and protein kinase G (PKG) inhibitors. Phosphoinositide hydrolysis was enhanced by CNP at all concentrations and abolished by U-73122. At 1 and 10 pM, CNP did not affect cAMP or guanosine 3′,5′-cyclic monophosphate (cGMP) levels, but at higher concentrations it increased cGMP and diminished cAMP content. Present findings show that CNP stimulated amylase release through the activation of NPR-C receptors coupled to the PLC pathway and downstream effectors involved in exocytosis. The attenuation of amylase release was likely related to cAMP reduction. The augmentation in cGMP supports activation of NPR-A/NPR-B receptors probably involved in calcium influx. Present findings give evidence that CNP is a potential direct regulator of pancreatic function.

AB - Several studies show that C-type natriuretic peptide (CNP) has a modulatory role in the digestive system. CNP administration reduces both jejunal fluid and bile secretion in the rat. In the present study we evaluated the effect of CNP on amylase release in isolated pancreatic acini as well as the receptors and intracellular pathways involved. Results showed that all natriuretic peptide receptors were expressed not only in the whole pancreas but also in isolated pancreatic acini. CNP stimulated amylase secretion with a concentration- dependent biphasic response; maximum release was observed at 1 pM CNP, whereas higher concentrations gradually attenuated it. The response was mimicked by a selective natriuretic peptide receptor (NPR-C) agonist and inhibited by pertussis toxin, strongly supporting NPR-C receptor activation. CNP-evoked amylase release was abolished by U-73122 (PLC inhibitor) and 2-aminoethoxydiphenyl borate (2-APB) [an inositol 1,4,5-triphosphate (IP 3) receptor antagonist], partially inhibited by GF-109203X (PKC inhibitor), and unaltered by ryanodine or protein kinase A (PKA) and protein kinase G (PKG) inhibitors. Phosphoinositide hydrolysis was enhanced by CNP at all concentrations and abolished by U-73122. At 1 and 10 pM, CNP did not affect cAMP or guanosine 3′,5′-cyclic monophosphate (cGMP) levels, but at higher concentrations it increased cGMP and diminished cAMP content. Present findings show that CNP stimulated amylase release through the activation of NPR-C receptors coupled to the PLC pathway and downstream effectors involved in exocytosis. The attenuation of amylase release was likely related to cAMP reduction. The augmentation in cGMP supports activation of NPR-A/NPR-B receptors probably involved in calcium influx. Present findings give evidence that CNP is a potential direct regulator of pancreatic function.

KW - Amylase secretion

KW - Natriuretic peptide receptors

KW - Phospholipase C

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=36148998003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36148998003&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00268.2007

DO - 10.1152/ajpgi.00268.2007

M3 - Article

VL - 293

JO - American journal of physiology. Gastrointestinal and liver physiology

JF - American journal of physiology. Gastrointestinal and liver physiology

SN - 0193-1857

IS - 5

ER -