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.