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Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

Lookup NU author(s): Dr Michael Gray, Professor Barry Argent


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The stimulatory pathways controlling HCO3- secretion by the pancreatic ductal epithelium are well described. However, only a few data are available concerning inhibitory mechanisms, which may play an important role in the physiological control of the pancreas. The aim of this study was to investigate the cellular mechanism by which substance P (SP) inhibits pancreatic ductal HCO3- secretion. Small intra/interlobular ducts were isolated from the pancreas of guinea pigs. During overnight culture the ducts seal to form a closed sac. Transmembrane HCO3- fluxes were calculated from changes in intracellular pH (measured using the pH-sensitive dye BCECF) and the buffering capacity of the cells. We found that secretin can stimulate HCO3- secretion in guinea pig pancreatic ducts about fivefold and that this effect could be totally blocked by SP. The inhibitory effect of SP was relieved by spantide, an SP receptor antagonist. SP had no effect on the activity of basolateral Na+-HCO3- cotransporters and Na+/H+ exchangers. However, the peptide did inhibit a Cl-dependent HCO3- efflux (secretory) mechanism, most probably the Cl-/HCO3- exchanger on the apical membrane of the duct cell.

Publication metadata

Author(s): Hegyi P, Gray MA, Argent BE

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology - Cell Physiology

Year: 2003

Volume: 285

Issue: 2

Pages: C268-C276

ISSN (print): 0363-6143

ISSN (electronic): 1522-1563

Publisher: American Physiological Society

PubMed id: 12672654


Funder referenceFunder name
068096Wellcome Trust