Specific age-dependence in capacity-limited uptake of propranolol by isolated rat lung

To investigate the effect of age on the pulmonary uptake of propranolol, minced tissue (0.4 g) of lungs isolated from 3- to 104-week-old rats was incubated with the drug (1 to 500 micrograms mL-1) prepared in oxygenated, pH 7.4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BSA for 60 min at 37 degrees C. In any age-group the metabolism of propranolol was not significant (i.e. less than 0.6% of any initial load) under the present in-vitro conditions. The extent of uptake after the incubation with 2.5 micrograms mL-1 of the drug was largest in the 7 weeks (i.e. 82% of the initial load) and relatively small in the 3(64%), 24(61%), 52(51%) and 104(48%) week old rats. Similar, specific age-dependence was observed in the tissue-to-medium concentration ratio of the drug. In any age-group, the initial uptake rate obtained in the first 5 min of the incubation was found to be a combination of apparently linear transport and saturable (capacity-limited) processes. There was a marked, specific age-dependence in the capacity-limited uptake rate. Although Km' value was almost equivalent in any age-group (i.e. 24.4 to 25.4 micrograms mL-1), Vmax exhibited a specific age-dependence by yielding the highest value in 7 weeks (0.726 +/- 0.101 mg g-1 min-1) and relatively low values in 3 (0.501 +/- 0.082 mg g-1 min-1), 52 (0.410 +/- 0.088 mg-1 g-1 min-1) and 104 (0.397 +/- 0.074 mg g-1 min-1) weeks.