The reserpine-treated rat as an experimental animal model for cystic fibrosis: abnormal Cl transport in pancreatic acinar cells.
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 microM) and caerulein (10 nM), but not by 10 nM vasointestinal peptide or 10 microM 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 suggest 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Martinez
J R
JR
Department of Child Health, University of Missouri School of Medicine, Columbia 65212.
Martinez
A M
AM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002108:Ceruletide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D005665:Furosemide / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D002712:Chlorides; D005576:Colforsin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D014660:Vasoactive Intestinal Peptide; D000584:Amiloride; D005665:Furosemide; D002108:Ceruletide; D012110:Reserpine; D000109:Acetylcholine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid