Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger.
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.
Hegyi
Peter
P
Department of Physiological Sciences, University Medical School, Newcastle upon Tyne NE2 4HH, UK.
Gray
Michael A
MA
Argent
Barry E
BE
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005452:Fluoresceins; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012633:Secretin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D005452:Fluoresceins; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D012633:Secretin; D013373:Substance P; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; C042867:spantide