Bicarbonate secretion in interlobular ducts from guinea‐pig pancreas.

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Abstract
1. The transport of HCO3‐ across the luminal membrane of pancreatic duct cells was studied by monitoring the luminal pH of isolated guinea‐pig interlobular ducts after microinjection of an extracellular fluoroprobe, the dextran conjugate of 2'7'‐bis(2‐carboxyethyl)‐5(6)‐carboxyfluorescein (BCECF‐dextran). Luminal Cl‐ concentration was also measured by microfluorometry following microinjection of the dextran conjugates of 6‐methoxy‐N‐(4‐aminoalkyl)quinolinium bromide (ABQ‐dextran) and Cl‐NERF (Cl‐NERF‐dextran). 2. When HCO3‐/CO2 was admitted to the bath, a transient acidification of the duct lumen was observed, followed by a marked alkalinization. The latter was abolished when the luminal Cl‐ concentration was reduced to 25‐35 mM by replacement with glucuronate and may, therefore, be attributed to Cl(‐)‐HCO3‐ exchange at the luminal membrane. 3. Secretin, forskolin and acetylcholine stimulated HCO3‐ secretion into the lumen even when the luminal Cl‐ concentration was reduced to approximately 7 mM. Furthermore, agonist‐evoked HCO3‐ secretion was not inhibited by luminal glibenclamide, dihydro‐4,4'‐diisothiocyanostilbene‐2,2'‐disulphonic acid (H2DIDS) or 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid (NPPB). These observations are not easily reconciled with HCO3‐ transport across the luminal membrane being mediated by Cl(‐)‐HCO3‐ exchange in parallel with a Cl‐ conductance. 4. Agonist‐stimulated HCO3‐ secretion was blocked by omitting Na+ from the bath but not by addition of N‐methyl‐N‐isobutylamiloride (MIA) or bafilomycin A1. This supports our previous conclusion that HCO3‐ entry into duct cells from the extracellular fluid requires Na+ but is not dependent on Na(+)‐H+ exchange or vacuolar‐type H(+)‐ATPase activity. 5. The three actions of secretin on guinea‐pig pancreatic duct cells described in this and the accompanying paper ‐ stimulation of a relatively Cl(‐)‐insensitive luminal HCO3‐ efflux pathway, stimulation of basolateral Na(+)‐HCO3‐ cotransport, and lack of effect on intracellular pH‐ require the current model of pancreatic HCO3‐ secretion to be modified.