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Fluid secretion in interlobular ducts isolated from guinea‐pig pancreas

1998; Wiley; Volume: 511; Issue: 2 Linguagem: Inglês

10.1111/j.1469-7793.1998.407bh.x

1469-7793

Hiroshi Ishiguro, Satoru Naruse, Martin C. Steward, Motoji Kitagawa, Shigeru B. H. Ko, T Hayakawa, R. M. Case∥,

Cannabis and Cannabinoid Research

Pancreatic HCO 3 − and fluid secretion were studied by monitoring luminal pH (pH L ) and luminal volume simultaneously in interlobular duct segments isolated from guinea‐pig pancreas. The secretory rate and HCO 3 − flux were estimated from fluorescence images obtained following microinjection of BCECF‐dextran (70 kDa, 20 μM) into the duct lumen. Ducts filled initially with a Cl − ‐rich solution swelled steadily (2.0 nl min −1 mm − 2 ) when HCO 3 − /CO 2 was introduced, and the luminal pH increased to 8.08. When Cl − was replaced by glucuronate, spontaneous fluid secretion was reduced by 75 %, and pH L did not rise above 7.3. Cl − ‐dependent spontaneous secretion was largely blocked by luminal H 2 DIDS (500 μM). We conclude that, in unstimulated ducts, HCO 3 − transport across the luminal membrane is probably mediated by Cl − ‐HCO 3 − exchange. Secretin (10 nM) and forskolin (1 μM) both stimulated HCO 3 − and fluid secretion. The final value of pH L (8.4) and the increase in secretory rate (1.5 nl min −1 mm − 2 ) after secretin stimulation were unaffected by substitution of Cl − . The Cl − ‐independent component of secretin‐evoked secretion was not affected by luminal H 2 DIDS. This suggests that a Cl − ‐independent mechanism provides the main pathway for luminal HCO 3 − transport in secretin‐stimulated ducts. Ducts filled initially with a HCO 3 − ‐rich fluid (125 mM HCO 3 − , 23 mM Cl − ) secreted a Cl − ‐rich fluid while unstimulated. This became HCO 3 − ‐rich when secretin was applied. Addition of H 2 DIDS and MIA (10 μM) to the bath reduced the secretory rate by 56 and 18 %, respectively. Applied together they completely blocked fluid secretion. We conclude that basolateral HCO 3 − transport is mediated mainly by Na + ‐HCO 3 − cotransport rather than by Na + ‐H + exchange.