Abstract
ABSTRACT: Pancreatic acini of control and reserpine-treated rats were incubated with the isotopic tracer 36Cl to compare Cl accumulation in the absence and presence of secretagogues and transport inhibitors. Two phases of Cl accumulation were ascertained in resting control cells: an initial rate (0–5 min) and a steady state level (10–30 min) of accumulation. Both phases were enhanced by acetylcholine (1 μM) and caerulein (10 nM), but not by 10 nM vasointestinal peptide or 10 μM forskolin. Exposure to 1 mM DIDS (4,4′-diisothiocyano-2,2′-stilbene disulfonic acid) inhibited both phases of Cl accumulation, whereas exposure to 1 mM amiloride had a delayed effect on the initial rate and reduced the steady state phase in both resting (unstimulated) or acetylcholine-stimulated cells. Furosemide (1 mM) had no effect on Cl accumulation when added to the cells just before tracer, but reduced it when added 10 min before. Neither the initial phase nor the steady state level of Cl accumulation were enhanced by acetylcholine in acini of reserpine-treated rats and the effect of DIDS on the initial phase was smaller than in control cells. Continued exposure to this inhibitor resulted, furthermore, in a significantly larger steady state Cl content. The inhibitory effects of amiloride and of a 10-min preincubation with furosemide were similar to those observed in control cells. These results sanest that Cl accumulates in rat pancreatic acini by way of DIDS-sensitive mechanisms that are activated by Ca2+-mediated, but not by cAMP-mediated, secretagogues. These mechanisms are altered in acini of reserpine-treated rats. Those responsible for the early (initial) phase are made insensitive to secretagogues but retain some sensitivity to DIDS. Mechanisms responsible for the maintenance of the steady state level are also altered as suggested by the paradoxical effect of DIDS. As this inhibitor blocks Cl conductances and Cl/HCO3 exchange, either or both of these transport mechanisms may be altered after chronic reserpine. This alteration can explain the reduced in vivo pancreatic fluid secretion observed in the treated animals, as pancreatic fluid secretion is Cl-dependent in the rat. The reserpine-treated rat is an experimental model of cystic fibrosis and a similar defect in Cl transport may also underlie the reduced pancreatic fluid secretion observed in this disease. A generalized defect in Cl transport may be present in exocrine cells of CF patients and of the animal model, involving alterations in the interaction of membrane transport mechanisms with regulatory molecules activated by tissue-specific second messengers.
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Ricardo Martinez, J., Martinez, A. The Reserpine-Treated Rat as an Experimental Animal Model for Cystic Fibrosis: Abnormal Cl Transport in Pancreatic Acinar Cells. Pediatr Res 24, 427–432 (1988). https://doi.org/10.1203/00006450-198810000-00002
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DOI: https://doi.org/10.1203/00006450-198810000-00002
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