Energy-dependent uptake of benzomorphans by leukocytes

Pentazocine rapidly enters the brain after i.p. administration to rats. Using leukocytes as model mammalian cells, the uptake of this drug was studied. Morphologically intact and metabolically active rat leukocytes accumulated pentazocine in vitro against a concentration gradient. The 6- to 10-fold concentration of the drug was dependent upon the presence of glucose in the incubation medium and was strongly affected by metabolic inhibitors present in millimolar concentrations. The uptake showed saturation kinetics in the concentration range of 1.7-14 x 10-5 M pentazocine and was competitively inhibited by analogue benzomorphan derivatives. Ouabain as well as sodium-free extracellular media had no effect on the uptake of pentazocine. The transport system for pentazocine in the leukocyte apparently differs from the relatively nonspecific amine pump which accumulates various organic bases in the blood platelet.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34100/1/0000382.pd

Transport and interaction of drugs in leukocytes

The accumulation of selected CNS drugs by rat leukocytes was previously reported. This paper presents evidence for the transport into leukocytes of additional drugs. Also studied was the inhibition of the latter processes by various structurally related compounds. The markedly rapid and sodium-independent uptakes into rat leukocytes of amphetamine, codeine, methadone and naloxone fulfilled the basic criteria for active transport. The uptake of morphine was apparently accomplished by more than one process. The affinities of the high capacity transport systems (approximate Vmax: 100 nmoles/g cells/5sec) varied considerably as reflected by the two extreme Km values obtained for methadone (20 [mu]M) and morphine (1.8 mM). A variety of amines inhibited the cellular transport of the drugs. Most potent inhibitors were quinacrine (Ki: 0.5 to 3 [mu]M), desipramine (Ki: 6-20 [mu]M) and methadone (Ki: 18-25 [mu]M). Morphine and tryptamine exhibited inhibition constants higher than 1 mM. The cellular transport processes newly described in rat leukocytes apparently represent a novel addition to the heterogenous biological transport of basic amines. The structural specificity of amine transport in various tissues is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22249/1/0000685.pd