Effect of morphine on mesangial immunoglobulin G aggregate kinetics.
Because mesangial expansion is considered a precursor of focal glomerulosclerosis, we studied whether morphine can cause mesangial expansion. We used radiolabeled human immunoglobulin G aggregates (125I-ahIgG) to study mesangial kinetics in control and experimental (morphine-treated) rats. Control and experimental rats were administered 125I-ahIgG by tail vein. Serum levels of 125I-ahIgG and uptake of 125I-ahIgG by liver, spleen, and mesangium were determined at 4, 8, 12, 24, and 36 h after 125I-ahIgG administration. Mesangial 125I-ahIgG levels were higher (P < 0.05) at 4 h and at later periods in morphine-treated vs. control rats. Naloxone, an opioid antagonist, did not attenuate the morphine-induced mesangial accumulation of 125I-ahIgG. The mean uptake of IgG aggregates was lower in the liver and spleen of morphine-treated rats at 36 h (P < 0.05). In both in vivo and in vitro experiments, ultrastructural studies showed accumulation of IgG-coated gold particles in vesicles, endosomes, and lysosomes. Morphine may have increased the accumulation of 125I-ahIgG in the glomeruli either by increasing the delivery of macromolecules into the mesangium or by altering the exit of macromolecules from the mesangium.
Singhal
P C
PC
Department of Medicine and Pathology, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Pan
C Q
CQ
Gibbons
N
N
Valderrama
E
E
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D005920:Glomerular Mesangium / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D009270:Naloxone; D009020:Morphine