Am J Physiol Cell Physiol Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 288: C1030-C1041, 2005. First published December 29, 2004; doi:10.1152/ajpcell.00430.2003
0363-6143/05 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/5/C1030    most recent
00430.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hegyi, P.
Right arrow Articles by Argent, B. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hegyi, P.
Right arrow Articles by Argent, B. E.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Protein kinase C mediates the inhibitory effect of substance P on HCO3– secretion from guinea pig pancreatic ducts

Péter Hegyi,1,2 Zoltán Rakonczay, Jr.,1,2 László Tiszlavicz,3 András Varró,4 András Tóth,4 Gábor Rácz,5 Gábor Varga,5 Michael A. Gray,2 and Barry E. Argent2

1First Department of Medicine, 3Department of Pathology, and 4Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary; 2Institute for Cell & Molecular Biosciences, University of Newcastle Medical School, Newcastle upon Tyne, United Kingdom; and 5Molecular Oral Biology Research Group, Department of Oral Biology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

Submitted 6 January 2003 ; accepted in final form 10 December 2004

The inhibitory control of pancreatic ductal HCO3– secretion may be physiologically important in terms of limiting the hydrostatic pressure developed within the ducts and in terms of switching off pancreatic secretion after a meal. Substance P (SP) inhibits secretin-stimulated HCO3– secretion by modulating a Cl–-dependent HCO3– efflux step at the apical membrane of the duct cell (Hegyi P, Gray MA, and Argent BE. Am J Physiol Cell Physiol 285: C268–C276, 2003). In the present study, we have shown that SP is present in periductal nerves within the guinea pig pancreas, that PKC mediates the effect of SP, and that SP inhibits an anion exchanger on the luminal membrane of the duct cell. Secretin (10 nM) stimulated HCO3– secretion by sealed, nonperfused, ducts about threefold, and this effect was totally inhibited by SP (20 nM). Phorbol 12,13-dibutyrate (PDBu; 100 nM), an activator of PKC, reduced basal HCO3– secretion by ~40% and totally blocked secretin-stimulated secretion. In addition, bisindolylmaleimide I (1 nM to 1 µM), an inhibitor of PKC, relieved the inhibitory effect of SP on secretin-stimulated HCO3– secretion and also reversed the inhibitory effect of PDBu. Western blot analysis revealed that guinea pig pancreatic ducts express the {alpha}-, {beta}I-, {delta}-, {epsilon}-, {eta}-, {theta}-, {zeta}-, and µ-isoforms of PKC. In microperfused ducts, luminal H2DIDS (0.5 mM) caused intracellular pH to alkalinize and, like SP, inhibited basal and secretin-stimulated HCO3– secretion. SP did not inhibit secretion further when H2DIDS was present in the lumen, suggesting that SP and H2DIDS both inhibit the activity of an anion exchanger on the luminal membrane of the duct cell.

pancreas; Cl–/HCO3– exchanger; inhibition; epithelium


Address for reprint requests and other correspondence: B. E. Argent, Institute for Cell and Molecular Biosciences, Univ. of Newcastle Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom (E-mail: b.e.argent{at}ncl.ac.uk)




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. K. Stewart, A. Yamamoto, M. Nakakuki, T. Kondo, S. L. Alper, and H. Ishiguro
Functional coupling of apical Cl-/HCO3- exchange with CFTR in stimulated HCO3- secretion by guinea pig interlobular pancreatic duct
Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1307 - G1317.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
V Venglovecz, Z Rakonczay Jr, B Ozsvari, T Takacs, J Lonovics, A Varro, M A Gray, B E Argent, and P Hegyi
Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig
Gut, August 1, 2008; 57(8): 1102 - 1112.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
M. R. Dorwart, N. Shcheynikov, D. Yang, and S. Muallem
The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport
Physiology, April 1, 2008; 23(2): 104 - 114.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. A. Hassan, S. Mentone, L. P. Karniski, V. M. Rajendran, and P. S. Aronson
Regulation of anion exchanger Slc26a6 by protein kinase C
Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1485 - C1492.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.