Anionic basis of fluid secretion by rat pancreatic acini in vitro.
Acinar secretion was studied in the caerulein-stimulated perfused rat pancreas. Unstimulated glands secreted at a mean basal rate of 1.1 microliters X g-1 X min-1 (SD = 0.74), which was not altered by perfusate anion substitution or by transport-blocking drugs. Caerulein evoked a maximum response (6.8 microliter X g-1 X min-1, SE = 0.36, n = 8) at a concentration of 18 pmol/l. Replacement of perfusate bicarbonate with either chloride or acetate did not significantly alter the stimulated secretory rate. In contrast, replacement with acetate of either chloride alone or chloride and bicarbonate reduced the rate of stimulated secretion by 75-80%, and replacement with isethionate abolished the response altogether. In glands perfused with solutions containing chloride but not bicarbonate, furosemide (10(-5) M), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS, 10(-4) M), amiloride (10(-4) M), and methazolamide (10(-4) M) all reduced the secretory response by more than 70%. When bicarbonate was included in the perfusate, the inhibitory effects for the same doses of blockers were much less, and except for methazolamide the same level of maximum inhibition was obtained when the blocker doses were increased 10-fold. The results suggest that rat pancreatic acini utilize a different secretory mechanism from the sodium chloride-carrying symport postulated to be most important in rat mandibular glands. The simplest model to explain our results would involve paired, basolateral antiports for Na-H and Cl-HCO3 exchange. We cannot exclude the presence of a Na-Cl symport, but if present, its role appears to be minor.
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism*; D002108:Ceruletide / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D066298:In Vitro Techniques; D007513:Isethionic Acid / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D000838:Anions; D000963:Antimetabolites; D002712:Chlorides; D002108:Ceruletide; D007513:Isethionic Acid