Uptake and release of 14C-morphine by pulmonary endothelium and cultured pulmonary endothelial cells.
1. Isolated perfused rabbit lungs and cultured pulmonary endothelial cells take up radiolabeled [14C]morphine in proportion to the amount of labeled drug in the medium. 2. The accumulated label is readily released from the isolated lungs by perfusion with unlabeled morphine or naloxone, but not by perfusion with Krebs-Ringer solution, sucrose or thiopental. 3. Thiourea also enhances efflux of radioactivity, suggesting that the release is not related to interaction with specific opiate receptors. 4. Uptake of [14C]morphine by cultured rabbit or human endothelial cells is unaffected by morphine or naloxone, and the release of radioactivity is not enhanced by these agents. 5. None of the drugs used caused pulmonary edema in the isolated lung preparation, and they did not cause the release of lactic dehydrogenase from cultured endothelial cells. 6. It is concluded that morphine can be taken up by pulmonary endothelium, but it is probably not bound to specific receptors, and it does not injure the endothelial cells.
D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000378:metabolism* / Q000633:toxicity; D011817:Rabbits
D009020:Morphine; D007770:L-Lactate Dehydrogenase