Morphine modulates cathepsin B and L activity in isolated glomeruli and mesangial cells.

Altered matrix degradation may be playing a role in the development of initial mesangial expansion and subsequent glomerulosclerosis in persons with heroin abuse. We studied whether morphine, a metabolite of heroin, had any effect on lysosomal content of cathepsin B and L in mesangial cells. Morphine (10(-6) M) increased (P < 0.01) mesangial cathepsin B and L activity (control, 22.1 + 2.2 vs. morphine, 31.4 + 1.4 mol NMec/microgram protein, N = 5). Morphine (10(-6) M) also increased (P < 0.01) glomerular cathepsin B and L activity (control, 0.1 + 0.01 vs. morphine, 2.2 +/- 0.2 pmol NMec/microgram protein, N = 3). This effect of morphine occurred in a dose-dependent manner. These results suggest that morphine enhances cathepsin B and L activity in mesangial cells and isolated glomeruli. This effect of morphine may enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules.