Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Biol. Chem. 284 (8): 4815-4822

© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Purinergic P2X7 Receptors Mediate ATP-induced Saliva Secretion by the Mouse Submandibular Gland*

Tetsuji Nakamoto{ddagger}§12, David A. Brown{ddagger}1, Marcelo A. Catalán{ddagger}1, Mireya Gonzalez-Begne{ddagger}, Victor G. Romanenko{ddagger}§, , and James E. Melvin{ddagger}§3

{ddagger}Center for Oral Biology and the §Department of Pharmacology & Physiology, University of Rochester Medical Center, Rochester, New York 14642

Abstract: Salivary glands express multiple isoforms of P2X and P2Y nucleotide receptors, but their in vivo physiological roles are unclear. P2 receptor agonists induced salivation in an ex vivo submandibular gland preparation. The nucleotide selectivity sequence of the secretion response was BzATP >> ATP > ADP >> UTP, and removal of external Ca2+ dramatically suppressed the initial ATP-induced fluid secretion (~85%). Together, these results suggested that P2X receptors are the major purinergic receptor subfamily involved in the fluid secretion process. Mice with targeted disruption of the P2X7 gene were used to evaluate the role of the P2X7 receptor in nucleotide-evoked fluid secretion. P2X7 receptor protein and BzATP-activated inward cation currents were absent, and importantly, purinergic receptor agonist-stimulated salivation was suppressed by more than 70% in submandibular glands from P2X7-null mice. Consistent with these observations, the ATP-induced increases in [Ca2+]i were nearly abolished in P2X7–/– submandibular acinar and duct cells. ATP appeared to also act through the P2X7 receptor to inhibit muscarinic-induced fluid secretion. These results demonstrate that the ATP-sensitive P2X7 receptor regulates fluid secretion in the mouse submandibular gland.


Received for publication November 12, 2008.

* This work was supported, in whole or in part, by National Institutes of Health Grants DE09692 and DE08921 (to J. E. M.) and NIDCR Training Grant T32-DE07202 (to D. A. B. and M. G.-B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 These authors contributed equally to this work.

2 Present address: Dept. of Oral Reconstruction and Rehabilitation, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu City 803-8580, Japan.

3 To whom correspondence should be addressed: Center for Oral Biology, Box 611, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642. Tel.: 585-275-3441; Fax: 585-506-0190; E-mail: james_melvin{at}urmc.rochester.edu.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
TRPV4 activation in mouse submandibular gland modulates Ca2+ influx and salivation.
Y. Zhang, M. A. Catalan, and J. E. Melvin (2012)
Am J Physiol Gastrointest Liver Physiol 303, G1365-G1372
   Abstract »    Full Text »    PDF »
P2X7 receptor activation induces inflammatory responses in salivary gland epithelium.
L. T. Woods, J. M. Camden, J. M. Batek, M. J. Petris, L. Erb, and G. A. Weisman (2012)
Am J Physiol Cell Physiol 303, C790-C801
   Abstract »    Full Text »    PDF »
Distinct contributions by ionotropic purinoceptor subtypes to ATP-evoked calcium signals in mouse parotid acinar cells.
S. Bhattacharya, D. S. Verrill, K. M. Carbone, S. Brown, D. I. Yule, and D. R. Giovannucci (2012)
J. Physiol. 590, 2721-2737
   Abstract »    Full Text »    PDF »
Distinct regulation by lipopolysaccharides of the expression of interleukin-1{beta} by murine macrophages and salivary glands.
M. Seil, M. E. Ouaaliti, S. Abdou Foumekoye, S. Pochet, and J. Dehaye (2012)
Innate Immunity 18, 14-24
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCOFormula Secretion.
M. G. Lee, E. Ohana, H. W. Park, D. Yang, and S. Muallem (2012)
Physiol Rev 92, 39-74
   Abstract »    Full Text »    PDF »
Cholinergic Agonists Activate P2X7 Receptors to Stimulate Protein Secretion by the Rat Lacrimal Gland.
D. A. Dartt and R. R. Hodges (2011)
Invest. Ophthalmol. Vis. Sci. 52, 3381-3390
   Abstract »    Full Text »    PDF »
Ectonucleotidases in the digestive system: focus on NTPDase3 localization.
E. G. Lavoie, B. D. Gulbransen, M. Martin-Satue, E. Aliagas, K. A. Sharkey, and J. Sevigny (2011)
Am J Physiol Gastrointest Liver Physiol 300, G608-G620
   Abstract »    Full Text »    PDF »
Residues 155 and 348 Contribute to the Determination of P2X7 Receptor Function via Distinct Mechanisms Revealed by Single-nucleotide Polymorphisms.
H. J. Bradley, J. M. Baldwin, G. R. Goli, B. Johnson, J. Zou, A. Sivaprasadarao, S. A. Baldwin, and L.-H. Jiang (2011)
J. Biol. Chem. 286, 8176-8187
   Abstract »    Full Text »    PDF »
Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands.
I. Novak, I. M. Jans, and L. Wohlfahrt (2010)
J. Physiol. 588, 3615-3627
   Abstract »    Full Text »    PDF »
Tmem16A Encodes the Ca2+-activated Cl- Channel in Mouse Submandibular Salivary Gland Acinar Cells.
V. G. Romanenko, M. A. Catalan, D. A. Brown, I. Putzier, H. C. Hartzell, A. D. Marmorstein, M. Gonzalez-Begne, J. R. Rock, B. D. Harfe, and J. E. Melvin (2010)
J. Biol. Chem. 285, 12990-13001
   Abstract »    Full Text »    PDF »
Characterization of P2X7 Purinergic Receptors and Their Function in Rat Lacrimal Gland.
R. R. Hodges, J. Vrouvlianis, M. A. Shatos, and D. A. Dartt (2009)
Invest. Ophthalmol. Vis. Sci. 50, 5681-5689
   Abstract »    Full Text »    PDF »
Spontaneous oscillations in intracellular Ca2+ concentration via purinergic receptors elicit transient cell swelling in rat parotid ducts.
A. Shitara, A. Tanimura, A. Sato, and Y. Tojyo (2009)
Am J Physiol Gastrointest Liver Physiol 297, G1198-G1205
   Abstract »    Full Text »    PDF »
Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia.
G. Casas-Pruneda, J. P. Reyes, G. Perez-Flores, P. Perez-Cornejo, and J. Arreola (2009)
J. Physiol. 587, 2887-2901
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882