Transport of narcotic analgesics by choroid plexus and kidney tissue in vitro

Abstract

Radioactive narcotic analgesics, including morphine, dihydromorphine, nalorphine, codeine, levorphan, dextrorphan, and l-methorphan were accumulated against an apparent concentration gradient in pieces of rabbit and dog choroid plexus and in slices of dog renal cortex by a metabolically dependent mechanism. The uptake of dihydromorphine by these tissues in vitro was a saturable process depressed by low temperatures, a nitrogen atmosphere, and certain metabolic inhibitors. It also was competitively inhibited by nalorphine and by any one of several organic bases which previously have been demonstrated to be actively transported by these tissues. Under certain conditions, stimulation of dihydromorphine uptake by choroid plexus was produced by organic bases. The transport in choroid plexus of one of these organic bases, hexamethonium, was competitively inhibited by dihydromorphine. Studies with levorphan and dextrophan indicated an element of stereospecificity in their accumulation by choroid plexus. Thus it is concluded that the narcotic analgesics share the same active transport mechanisms described for a variety of organic bases that are accumulated in choroid plexus and renal tissue in vitro. Suggestions are made relative to the significance of these observations for the intact animal.