THE TUBULAR TRANSPORT AND METABOLISM OF MORPHINE-N-METHYL-C¹⁴ BY THE CHICKEN KIDNEY

¹ Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana

The renal portal system of chickens was utilized to study the renal tubular transport and renal metabolism of morphine. An average apparent tubular excretion fraction of 29.5% was found for excreted radioactivity when tracer doses of morphine-C¹⁴ were infused and an average apparent tubular excretion fraction of 13.6% was determined for excreted radioactivity when 0.35 mg/kg/min of unlabeled morphine sulfate was infused with the tracer. The nature of the excreted radioactivity was charcterized by countercurrent distribution analyses. Two components were excreted, free morphine-C¹⁴ and a C¹⁴ metabolite. The metabolite was also excreted in excess by the infused kidney, which indicated that the metabolite had been formed by the kidney. Apparent tubular excretion fractions greater than 10% were found for the excreted free morphine. Cyanine 863, which blocks the base transport system, reduced the excretion of both free morphine and metabolite by the the infused kidney. Experiments using increasing doses of unlabeled morphine with a constant quantity of morphine-C¹⁴ indicated that a transport system was involved. We conclude that morphine is transported by the base transport system of the kidney and is metabolized by the renal tubular cells. It may be that transport into the cell precedes metabolism.

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