PubMed · 7903513
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J C Drummond. 1993. Are the data missing?. https://doi.org/10.1097/00000542-199312000-00055
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The binding and internalization of radioiodinated and fluorescent mu and delta opioid peptides in mammalian cells were quantitatively studied by biochemical techniques and directly visualized by confocal microscopy. The labeled peptides were prepared by inserting either a 125I-Bolton-Hunter group or a fluorescent probe into the C-terminal part of 5-aminopentylamide derivatives of deltorphin-I and [Lys7]dermorphin. The purified derivatives kept most of their specificity and selectivity toward delta and mu opioid receptors, respectively. Biochemical and confocal microscopy data showed that both mu and delta opioid peptides were internalized in mammalian cells transfected with the corresponding opioid receptor according to a receptor-mediated mechanism. The internalization process was time- and temperature-dependent and was completely blocked by the endocytosis inhibitor phenylarsine oxyde. Internalization of both delta and mu ligands occurred from a single large cap at one pole of the cell, indicating that polymerization of ligand-receptor complexes preceeded internalization. Finally, green and red fluorescent analogues of deltorphin-I and [Lys7]dermorphin, respectively, were found to internalize through partly distinct endocytic pathways in cells co-transfected with mu and delta receptors, suggesting that each of these receptors interacts with distinct proteins mediating intracellular sorting and trafficking.
PURPOSE: This study was performed to investigate the effects of morphine on the disposition of 5-fluorouracil (5-FU). METHODS: Mice were injected subcutaneously (s.c.) with saline or morphine, 20 mg/kg. 5-FU was administered intravenously (i.v.) 30 min later as a single bolus or by constant infusion. Blood samples were obtained by orbital sinus puncture. Urine samples were obtained from the bladder after ligation of the external urethra. 5-FU concentrations in plasma and urine were determined by HPLC. RESULTS: Morphine markedly elevated plasma levels of 5-FU given at doses of 100 to 860 mg/kg. The plasma clearance rate of a bolus dose of 100 mg/kg 5-FU was significantly reduced from 54 to 28 ml/min per kg and the elimination half-life was increased from 6.9 to 12.2 min by prior administration of morphine. When 5-FU was infused at 0.5 mg/kg per min, morphine reduced its plasma clearance rate from 145 to 94 ml/min per kg. Mice made tolerant by prior morphine administration required higher doses of this opiate to raise 5-FU levels as well as to cause analgesia. The effects of morphine on 5-FU disposition were antagonized by naltrexone. Excretion of 5-FU in urine was not affected by morphine treatment. CONCLUSIONS: The plasma clearance rate of 5-FU in mice is significantly reduced by concomitant use of morphine. This effect of morphine is due to reduced hepatic elimination of 5-FU rather than to a decrease in its renal excretion.
In vitro receptor autoradiography was used to localize sigma 1 receptors, sigma 2 receptors, and novel haloperidol/DTG-inaccessible sites for sigma and opiate ligands in rat spleen. Sigma-1 receptors were present throughout the spleen, but were most concentrated in the T cell zones. Binding under "sigma 2 receptor-selective' conditions was 70% nonspecific, and sigma 2 receptors could not be detected. Haloperidol/DTG-inaccessible sites had a coarse, punctate distribution in the red pulp and marginal zones of the white pulp. This anatomical localization suggests types of cells and functions that should be examined for modulation by sigma receptors.