SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion

P. Hegyi, Z. Rakonczay, L. Tiszlavicz, A. Varró, A. Tóth, Gábor Rácz, G. Varga, Michael A. Gray, Barry E. Argent

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Citations (Scopus)

Abstract

SLC26 anion exchangers (probably SLC26A3 and SLC26A6) are expressed on the apical membrane of pancreatic duct cells and play a key role in HCO 3 - secretion; a process that is inhibited by the neuropeptide, substance P (SP). SP had no effect on basolateral HCO 3 - transporters in the duct cell or on CFTR Cl- channels, but inhibited a Cl--dependent HCO3 - efflux step on the apical membrane. In microperfused ducts, luminal H 2DIDS (0.5 mM) caused intracellular pH to alkalinize (consistent with inhibition of HCO3 - efflux) and, like SP, inhibited HCO3 - secretion. SP did not reduce HCO3 - secretion further when H2DIDS was applied to the duct lumen, suggesting that SP and H2DIDS inhibit the same transporter on the apical membrane. As SLC26A6 is DIDS-sensitive, this isoform is the likely target for SP. The inhibitory effect of SP was mimicked by phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). Moreover, bisindolylmaleimide, a blocker of PKC, relieved the inhibitory effect of both SP and PDBu on HCO3 - secretion. Western blot analysis revealed that guinea pig pancreatic ducts express the α, β1, δ, ε, η, θ, ζ and μ isoforms of PKC. We conclude that PKC is a negative regulator of SLC26 activity in pancreatic duct cells.

Original languageEnglish
Title of host publicationNovartis Foundation Symposium
Pages164-173
Number of pages10
Volume273
Publication statusPublished - 2006

Publication series

NameNovartis Foundation Symposium
Volume273
ISSN (Print)15282511

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Substance P
Bicarbonates
Protein Kinase C
Pancreatic Ducts
Phorbol 12,13-Dibutyrate
Membranes
Protein Isoforms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Neuropeptides
Anions
Guinea Pigs
Western Blotting

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hegyi, P., Rakonczay, Z., Tiszlavicz, L., Varró, A., Tóth, A., Rácz, G., ... Argent, B. E. (2006). SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion. In Novartis Foundation Symposium (Vol. 273, pp. 164-173). (Novartis Foundation Symposium; Vol. 273).

SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion. / Hegyi, P.; Rakonczay, Z.; Tiszlavicz, L.; Varró, A.; Tóth, A.; Rácz, Gábor; Varga, G.; Gray, Michael A.; Argent, Barry E.

Novartis Foundation Symposium. Vol. 273 2006. p. 164-173 (Novartis Foundation Symposium; Vol. 273).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Hegyi, P, Rakonczay, Z, Tiszlavicz, L, Varró, A, Tóth, A, Rácz, G, Varga, G, Gray, MA & Argent, BE 2006, SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion. in Novartis Foundation Symposium. vol. 273, Novartis Foundation Symposium, vol. 273, pp. 164-173.
Hegyi P, Rakonczay Z, Tiszlavicz L, Varró A, Tóth A, Rácz G et al. SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion. In Novartis Foundation Symposium. Vol. 273. 2006. p. 164-173. (Novartis Foundation Symposium).
Hegyi, P. ; Rakonczay, Z. ; Tiszlavicz, L. ; Varró, A. ; Tóth, A. ; Rácz, Gábor ; Varga, G. ; Gray, Michael A. ; Argent, Barry E. / SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion. Novartis Foundation Symposium. Vol. 273 2006. pp. 164-173 (Novartis Foundation Symposium).
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AB - SLC26 anion exchangers (probably SLC26A3 and SLC26A6) are expressed on the apical membrane of pancreatic duct cells and play a key role in HCO 3 - secretion; a process that is inhibited by the neuropeptide, substance P (SP). SP had no effect on basolateral HCO 3 - transporters in the duct cell or on CFTR Cl- channels, but inhibited a Cl--dependent HCO3 - efflux step on the apical membrane. In microperfused ducts, luminal H 2DIDS (0.5 mM) caused intracellular pH to alkalinize (consistent with inhibition of HCO3 - efflux) and, like SP, inhibited HCO3 - secretion. SP did not reduce HCO3 - secretion further when H2DIDS was applied to the duct lumen, suggesting that SP and H2DIDS inhibit the same transporter on the apical membrane. As SLC26A6 is DIDS-sensitive, this isoform is the likely target for SP. The inhibitory effect of SP was mimicked by phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC). Moreover, bisindolylmaleimide, a blocker of PKC, relieved the inhibitory effect of both SP and PDBu on HCO3 - secretion. Western blot analysis revealed that guinea pig pancreatic ducts express the α, β1, δ, ε, η, θ, ζ and μ isoforms of PKC. We conclude that PKC is a negative regulator of SLC26 activity in pancreatic duct cells.

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