The chronically reserpinized rat as a model for cystic fibrosis: abnormal Cl- transport as the basis for reduced salivary fluid secretion.

Saliva secretion induced by 10(-6) M acetylcholine was reduced 74% in isolated, perfused submandibular glands of control rats when the gland was perfused with solutions containing either furosemide (10(-3) M) or sulfate (instead of chloride) as the major anion. In regular (Cl-containing) perfusates without furosemide, saliva secretion was reduced 74% in isolated glands of rats treated with seven intraperitoneal doses of reserpine (0.5 mg/kg body weight). In the latter, addition of furosemide or replacement of perfusate Cl- with SO = 4 caused a further 35% drop in saliva volumes. Salivary Cl- concentrations were lower in saliva from the treated animals and were reduced further by furosemide, which also reduced the Cl- concentrations of control saliva. In submandibular acini isolated from control glands, acute exposure to 36Cl (1 mu Ci/ml) resulted in a rapid uptake of tracer so that a constant content of isotope (approximately 9.5 nM/mg protein) was attained in 4-5 min and maintained for 30 min. This basal uptake reached 8.4 nM/mg protein in acini isolated from glands of reserpine-treated rats and attainment of a steady state of tracer content was delayed and required 8-10 min. Exposure to acetylcholine reduced uptake and steady state tracer content by 35% in control acini, but had no effect in acini of reserpine-treated rats. Acetylcholine caused a rapid decrease (42% in 1 min) in 36Cl content of control acini which were preloaded with tracer for 12 min, but only a 23% decrease in acini of reserpine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)