Abstract
The multidrug resistance (MDR) transport protein is a normal constituent of proximal renal tubules although its function has not been defined in vivo. We find that colchicine, an MDR substrate, is secreted into urine by a process which is distinct from the organic cation transporter responsible for tetraethylammonium and N-methylnicotinamide secretion. Cyclosporine (CsA), which reverses MDR in vitro presumably by inhibiting the MDR transporter, inhibits colchicine renal secretion but does not inhibit the net secretion of the organic cation, ranitidine, or the organic anion, p-aminohippurate. After CsA (2 mg/kg i.v.), colchicine renal clearance decreased from 6.23 ± 0.46 to 3.58 ± 0.31 ml/min · kg (P < .05), glomerular filtration rate was unchanged (4.21 ± 0.08 and 3.88 ± 0.17 ml/min · kg, before and after CsA, respectively; P = .09) and colchicine secretory ratio decreased from 1.48 ± 0.11 to 0.92 ± 0.07 (P < .05). Cremophor (CsA vehicle) increased colchicine renal clearance (6.77 ± 0.29 to 7.7 ± 0.3 ml/min · kg, P < .05) and colchicine secretory ratio (1.425 ± 0.071 to 1.621 ± 0.061, P < .05). The inhibition of colchicine secretion was long-lived lasting at least 30 hr after CsA. Thus, colchicine is actively secreted into urine by the multidrug transporter in vivo. CsA profoundly inhibits colchicine secretion into urine while having no effect on the secretion of the organic cation ranitidine or the organic anion p-aminohippurate.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 50-55 |
| Number of pages | 6 |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 261 |
| Issue number | 1 |
| State | Published - 1992 |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Effect of cyclosporine on colchicine secretion by the kidney multidrug transporter studied in vivo. / Speeg, Kermit V; Maldonado, A. L.; Liaci, J.; Muirhead, D.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 261, No. 1, 1992, p. 50-55.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of cyclosporine on colchicine secretion by the kidney multidrug transporter studied in vivo
AU - Speeg, Kermit V
AU - Maldonado, A. L.
AU - Liaci, J.
AU - Muirhead, D.
PY - 1992
Y1 - 1992
N2 - The multidrug resistance (MDR) transport protein is a normal constituent of proximal renal tubules although its function has not been defined in vivo. We find that colchicine, an MDR substrate, is secreted into urine by a process which is distinct from the organic cation transporter responsible for tetraethylammonium and N-methylnicotinamide secretion. Cyclosporine (CsA), which reverses MDR in vitro presumably by inhibiting the MDR transporter, inhibits colchicine renal secretion but does not inhibit the net secretion of the organic cation, ranitidine, or the organic anion, p-aminohippurate. After CsA (2 mg/kg i.v.), colchicine renal clearance decreased from 6.23 ± 0.46 to 3.58 ± 0.31 ml/min · kg (P < .05), glomerular filtration rate was unchanged (4.21 ± 0.08 and 3.88 ± 0.17 ml/min · kg, before and after CsA, respectively; P = .09) and colchicine secretory ratio decreased from 1.48 ± 0.11 to 0.92 ± 0.07 (P < .05). Cremophor (CsA vehicle) increased colchicine renal clearance (6.77 ± 0.29 to 7.7 ± 0.3 ml/min · kg, P < .05) and colchicine secretory ratio (1.425 ± 0.071 to 1.621 ± 0.061, P < .05). The inhibition of colchicine secretion was long-lived lasting at least 30 hr after CsA. Thus, colchicine is actively secreted into urine by the multidrug transporter in vivo. CsA profoundly inhibits colchicine secretion into urine while having no effect on the secretion of the organic cation ranitidine or the organic anion p-aminohippurate.
AB - The multidrug resistance (MDR) transport protein is a normal constituent of proximal renal tubules although its function has not been defined in vivo. We find that colchicine, an MDR substrate, is secreted into urine by a process which is distinct from the organic cation transporter responsible for tetraethylammonium and N-methylnicotinamide secretion. Cyclosporine (CsA), which reverses MDR in vitro presumably by inhibiting the MDR transporter, inhibits colchicine renal secretion but does not inhibit the net secretion of the organic cation, ranitidine, or the organic anion, p-aminohippurate. After CsA (2 mg/kg i.v.), colchicine renal clearance decreased from 6.23 ± 0.46 to 3.58 ± 0.31 ml/min · kg (P < .05), glomerular filtration rate was unchanged (4.21 ± 0.08 and 3.88 ± 0.17 ml/min · kg, before and after CsA, respectively; P = .09) and colchicine secretory ratio decreased from 1.48 ± 0.11 to 0.92 ± 0.07 (P < .05). Cremophor (CsA vehicle) increased colchicine renal clearance (6.77 ± 0.29 to 7.7 ± 0.3 ml/min · kg, P < .05) and colchicine secretory ratio (1.425 ± 0.071 to 1.621 ± 0.061, P < .05). The inhibition of colchicine secretion was long-lived lasting at least 30 hr after CsA. Thus, colchicine is actively secreted into urine by the multidrug transporter in vivo. CsA profoundly inhibits colchicine secretion into urine while having no effect on the secretion of the organic cation ranitidine or the organic anion p-aminohippurate.
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M3 - Article
C2 - 1348538
AN - SCOPUS:0026636982
VL - 261
SP - 50
EP - 55
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -