TRANSPORT AND METABOLISM OF [H-3]-LABELED MORPHINE IN ISOLATED, NONPERFUSED PROXIMAL TUBULAR SEGMENTS OF THE RABBIT KIDNEY

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (3) , 811-815
Abstract
Proximal tubular segments (S1, S2 and S3) of the rabit kidney were incubated in oxygenated Ringer''s solution (30 min, pH 7.4, 37.degree. C) containing bovine serum albumin (10 g/l) and [3H]morphine (0.7 .mu.M). The uptake, expressed as tissue water/medium ratio at equilibrium, for S1 was 42.2 .+-. 3.95 (mean .+-. SE), n = 16 tubules from 6 animals; for S2 41.6 .+-. 4.17, n = 18 tubules from 6 animals; and for S3, 29.0 .+-. 3.83, n = 15 tubules from 6 animals, a value significantly lower (P < 0.05) 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 h, 25.degree. C), all the recovered radiaoctivity 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%. There was no decrease in uptake in the presence of N1-methylnicotinamide (10-3 M). The whole proximal tubule is able to accumulate morphine by a specific transport system for organic cations, but part of this uptake might be due to cellular metabolism and intracellular drug binding.