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

Sabbatini, María Eugenia; Vatta, Marcelo S.; Davio, Carlos; Bianciotti, Liliana G.

doi:10.1152/ajpgi.00163.2006

Cited by 23 publications

(18 citation statements)

References 42 publications

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“…Under such conditions, Ͼ95% of acinar cells express adenoviral-driven proteins (4). In another experiment, acutely dissociated acini were incubated with or without pertussis toxin (2 g/ml) for 2 h at 37°C, as previously described (36).…”

Section: Methodsmentioning

confidence: 99%

CCK activates RhoA and Rac1 differentially through Gα₁₃ and Gα_q in mouse pancreatic acini

Sabbatini

Bi²,

Ji³

et al. 2010

American Journal of Physiology-Cell Physiology

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Cholecystokinin (CCK) has been shown to activate RhoA and Rac1, as well as reorganize the actin cytoskeleton and, thereby, modify acinar morphology and amylase secretion in mouse pancreatic acini. The aim of the present study was to determine which heterotrimeric G proteins activate RhoA and Rac1 upon CCK stimulation. Gα13, but not Gα12, was identified in mouse pancreatic acini by RT-PCR and Western blotting. Using specific assays for RhoA and Rac1 activation, we showed that only active Gα13 activated RhoA. By contrast, active Gα13 and Gαq, but not Gαs, slightly increased GTP-bound Rac1 levels. A greater increase in Rac1 activation was observed when active Gα13 and active Gαq were coexpressed. Gαi was not required for CCK-induced RhoA or Rac1 activation. The regulator of G protein signaling (RGS) domain of p115-Rho guanine nucleotide exchange factor (p115-RGS), a specific inhibitor of Gα12/13-mediated signaling, abolished CCK-stimulated RhoA activation. By contrast, both RGS-2, an inhibitor of Gαq, and p115-RGS abolished CCK-induced Rac1 activation, which was PLC pathway-independent. Active Gαq and Gα13, but not Gαs, induced morphological changes and actin redistribution similar to 1 nM CCK. CCK-induced actin cytoskeletal reorganization was inhibited by RGS-2, but not by p115-RGS, whereas CCK-induced amylase secretion was blocked by both inhibitors. Together, these findings indicate that, in mouse pancreatic acini, Gα13 links CCK stimulation to the activation of RhoA, whereas both Gα13 and Gαq link CCK stimulation to the activation of Rac1. CCK-induced actin cytoskeletal reorganization is mainly mediated by Gαq. By contrast, Gα13 and Gαq signaling are required for CCK-induced amylase secretion.

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Section: Methodsmentioning

confidence: 99%

CCK activates RhoA and Rac1 differentially through Gα₁₃ and Gα_q in mouse pancreatic acini

Sabbatini

Bi²,

Ji³

et al. 2010

American Journal of Physiology-Cell Physiology

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“…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).…”

Section: Measurement Of Campmentioning

confidence: 99%

“…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). MRP4 (ATP-binding cassette sub-family C member 4 [ABCC4]) is a member of the multidrug resistance proteins (MRPs) belonging to the C group of the ATP-binding cassette (ABC) protein superfamily, which functions as an energy-dependent, transmembrane efflux transporter.…”

Section: Introductionmentioning

confidence: 99%

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

Ventimiglia

Najenson

Perazzo

et al. 2015

Mol Med

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“…In theory, the function of this P2Y 2 receptor to BK interaction would be the "brake" or "control" point in regulation of secretion in the ductal system, perhaps sensing and preventing distension of the duct. Other mediators, such as substance P and atrial natriuretic factor, have been ascribed similar protective roles since they inhibit duct secretion [108,109].…”

Section: Pancreatic Acinimentioning

confidence: 99%

Purinergic receptors in the endocrine and exocrine pancreas

Novak

2007

Purinergic Signalling

115

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The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In β cells, stimulation of P2Y 1 receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y 1 receptors, there is also evidence for other P2 and adenosine receptors in β cells (P2Y 2 , P2Y 4 , P2Y 6 , P2X subtypes and A 1 receptors) and in glucagon-secreting α cells (P2X 7 , A 2 receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y 2 , P2Y 4 , P2Y 11 , P2X 4 and P2X 7 receptors could regulate secretion, primarily by affecting Cl − and K + channels and intracellular Ca 2+ signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases.

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

Abstract: Sabbatini ME, Vatta MS, Davio CA, Bianciotti LG. Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas.

Cited by 23 publications

References 42 publications

CCK activates RhoA and Rac1 differentially through Gα₁₃ and Gα_q in mouse pancreatic acini

CCK activates RhoA and Rac1 differentially through Gα₁₃ and Gα_q in mouse pancreatic acini

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

Purinergic receptors in the endocrine and exocrine pancreas

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

Abstract: Sabbatini ME, Vatta MS, Davio CA, Bianciotti LG. Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas.

Cited by 23 publications

References 42 publications

CCK activates RhoA and Rac1 differentially through Gα13 and Gαq in mouse pancreatic acini

CCK activates RhoA and Rac1 differentially through Gα13 and Gαq in mouse pancreatic acini

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

Purinergic receptors in the endocrine and exocrine pancreas

Contact Info

Product

Resources

About

CCK activates RhoA and Rac1 differentially through Gα₁₃ and Gα_q in mouse pancreatic acini

CCK activates RhoA and Rac1 differentially through Gα₁₃ and Gα_q in mouse pancreatic acini