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  • Title: Transport and metabolism of [3H]morphine in isolated, nonperfused proximal tubular segments of the rabbit kidney.
    Author: Schäli C, Roch-Ramel F.
    Journal: J Pharmacol Exp Ther; 1982 Dec; 223(3):811-5. PubMed ID: 7143242.
    Abstract:
    Proximal tubular segments (S1, S2 and S3) of the rabbit kidney were incubated in oxygenated Ringer's solution (30 min, pH 7.4, 37 degrees C) containing bovine serum albumin (10 g/l) and [3H]morphine (0.7 microM). The uptake, expressed as tissue water/medium ratio at equilibrium, for S1 was 42.2 +/- 3.95 (mean +/- S.E.), n = 16 tubules from six animals; for S2, 41.6 +/- 4.17, n = 18 tubules from six animals; and for S3, 29.0 +/- 3.83, n = 15 tubules from six animals, a value significantly lower (P less than .05) than in the S1 and S2 segment. High-performance liquid chromatography analysis of the accumulated tritium revealed metabolism of [3H]morphine. Unchanged morphine represented 35.5 +/- 3.4% of the total radioactivity recovered in the extract from S1 segments, 51.1 +/- 7.7% from S2 and 77.3 +/- 1.8 from S3 segments. After treating the tubular extracts with beta-glucuronidase (5 hr, 25 degrees C), all the recovered radioactivity represented unchanged morphine. The main metabolite, thus, was a glucuronide. KCN (10(-2) M), mepiperphenidol (Darstine, 10(-4) M) and quinine (10(-4) M) inhibited [3H]morphine uptake by 55-70%. Surprisingly, there was no decrease in uptake in the presence of N1-methylnicotinamide (10(-3) M). We conclude that the whole proximal tubule is able to accumulate morphine by a specific transport system for organic cations, but that part of this uptake might be due to cellular metabolism and intracellular binding of the drug.
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