Effects of metabolic inhibitors and incubation temperature on the saturable uptake of propranolol by isolated rat lung tissue.
The effects of several metabolic inhibitors (50 microM) on the initial uptake rate of propranolol (0.5 to 500 micrograms mL-1) by the minced lungs (0.4 g) isolated from 7-week-old rats has been investigated in oxygenated, pH 7.4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BSA at 37 degrees C for 5 min. The effect of the incubation temperature was also examined. Metabolism of propranolol was almost insignificant (i.e. less than 1.3% of the initial load). The overall initial uptake rate was considered to be a combination of apparent linear transport and saturable processes. For the control uptake rate, the linear transport rate constant was 1.26 +/- 0.16 g-1 mL-1 min-1, while Vmax and Km' of the capacity limited uptake process were estimated as 0.727 +/- 0.074 mg g-1 min-1 and 24.8 +/- 2.71 micrograms mL-1, respectively. No metabolic inhibitor tested had an effect on the linear transport rate of propranolol but 2,4-dinitrophenol and potassium cyanide inhibited saturable uptake rate (i.e. Vmax) of propranolol significantly (P less than 0.01) while ouabain, phloridine and iodoacetic acid did not do so significantly. Reduction of the incubation temperature to 15 degrees C decreased and at 25 degrees C tended to decrease, both linear transport and saturable uptake rates.
Iwamoto
K
K
Department of Pharmacy, Shimane Medical University Hospital, Izumo, Japan.
Watanabe
J
J
Yonekawa
H
H
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D000963:Antimetabolites; D011433:Propranolol