MORPHINE STIMULATES SUPEROXIDE FORMATION BY GLOMERULAR MESANGIAL CELLS

Focal glomerulosclerosis is the predominant glomerular lesion in heroi n addicts. We studied whether morphine, a metabolite of heroin, could directly affect the formation of superoxide by glomerular mesangial ce lls. Mesangial cells preincubated with morphine (10(-8) M) showed a hi gher(P < 0.001) production of super oxide when compared to control cel ls (control) 401 +/- 21 vs. morphine 610 +/- 41 nM/mg protein/h). This effect of morphine on mesangial cells was dose dependent. Naloxone, a n opiate antagonist, attenuated morphine-induced formation of superoxi de 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 pr otein/h]. We conclude that morphine enhances formation of superoxide b y mesangial cells and this effect of morphine seems to be mediated thr ough 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.