Morphine stimulates superoxide formation by glomerular mesangial cells.

Focal glomerulosclerosis is the predominant glomerular lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the formation of superoxide by glomerular mesangial cells. Mesangial cells preincubated with morphine (10(-8) M) showed a higher (P < 0.001) production of superoxide when compared to control cells (control) 401 +/- 21 vs. morphine 610 +/- 41 nM/mg protein/h). This effect of morphine on mesangial cells was dose dependent. Naloxone, an opiate antagonist, attenuated morphine-induced formation of superoxide by mesangial cells [control, 317 +/- 4; morphine (10(-8) M), 573 +/- 9; and naloxone (10(-8) M) + morphine (10(-8) M), 333 +/- 6 nM/mg protein/h]. We conclude that morphine enhances formation of superoxide by mesangial cells and this effect of morphine seems to be mediated through opiate receptors. Since superoxide has been demonstrated to cause mesangiolysis, we propose that morphine may be playing a role in the induction of mesangial injury in patients with opiate abuse.