Z Gastroenterol 2005; 43 - 41
DOI: 10.1055/s-2005-869688

The inhibitory effect of Substance P on HCO3- secretion from the guinea pig microperfused pancreatic ducts

P Hegyi 1, Z Rakonczay Jr 2, T Takács 1, J Papp 3, J Lonovics 1, A Varró 3, A Tóth 3, M Gray 2, B Argent 2
  • 1First Department of Medicine, Faculty of Medicine, University of Szeged, H-6720, Szeged, Hungary
  • 2Institute for Cell & Molecular Biosciences, University Medical School, Newcastle upon Tyne, NE2 4HH, UK
  • 3Department of Pharmacology and Pharmacotherapy, Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Faculty of Medicine, University of Szeged, H-6720, Szeged, Hungary

Background. We have previously shown using sealed, non-perfused, ducts that Substance P (SP) inhibits HCO3-secretion by inhibiting Cl-dependant HCO3-efflux on the luminal membrane of the duct cell (Hegyi et al. Am J Physiol Cell Physiol 285: C268-C276, 2003). However, in that study we had no direct evidence that SP affected a luminal anion exchanger. To address this issue we examined the effects of luminal H2DIDS on the inhibitory effect of SP in microperfused ducts.

Methods. Small intra/interlobular pancreatic ducts were isolated from guinea pigs. We microperfused the ducts allowing direct access to the luminal membrane of the duct cell. The rate of HCO3-secretion was determined by measuring the initial rate of intracellular acidification (using BCECF) following sudden block of basolateral NaHCO3 cotransporters and Na+/H+ exchangers with H2DIDS (500µM) and amiloride (200µM) respectively. The buffering capacity of duct cells was estimated and the rate of transmembrane H+ flux, J(H+), was calculated. Since H+ and HCO3- will largely be derived from H2CO3, we have assumed that J(H+) is equivalent to J(HCO3). All the experiments were performed in HCO3-buffered Ringer at 37°C.

Results. Rates of HCO3- secretion measured using the inhibitor stop method were about 2 fold higher in microperfused ducts as compared to sealed, non-perfused, ducts. Application of luminal H2DIDS (0.5 mM) caused intracellular pH to alkalinise 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 same transporter on the luminal membrane of the duct cell.

Conclusions. SP inhibits an H2DIDS-sensitive HCO3- transport step at the luminal membrane of the duct cell, most likely a member of the SLC26 family anion exchanger.

This work was supported by The Wellcome Trust and OTKA.