MORPHINE MODULATES 72-KDA MATRIX METALLOPROTEINASE

Mesangial expansion is considered to be a precursor of glomerulosclero sis, a predominant glomerular lesion in heroin nephropathy. In additio n to matrix synthesis, matrix degradation may also contribute to expan sion of mesangium. In this study, we evaluated the effect of morphine on metalloproteinases (gelatinases) that degrade type IV collagen and are secreted by mesangial cells (MC). Gelatinolytic activity was signi ficantly decreased in media of MC exposed to morphine for 1 wk compare d with control [control, 2,411.6 +/- 198.7; morphine (10(-6) M), 954.4 +/- 112.2 ng mg protein(-1).3 h(-1); P < 0.001]. A similar effect was seen at 2 wk [control, 17,010.6 +/- 1,789.5; morphine (10(-6) M), 8,9 25.2 +/- 1,623.5 ng.mg protein(-1) 3 h(-1); P < 0.02]. Percent change in gelatinolytic activity was 39.58% (1 wk) and 47.53% (2 wk) compared with control. Morphine at concentrations of 10(-10) to 10(-6) M decre ased gelatinolytic activity in MC. In in vivo studies, 24-h urines of morphine-treated rats showed a lower (P < 0.01) gelatinolytic activity when compared with controls. Isolated glomeruli from morphine-treated rats also showed decreased (P < 0.05) gelatinolytic activity compared with control. Naloxone, an opioid antagonist, did not inhibit the eff ect of morphine on gelatinolytic activity of MC. These results suggest that morphine may cause a decrease in degradation of type TV collagen in patients with heroin addiction. Accumulation of collagen because o f lack of gelatinolytic activity in the mesangium may contribute to th e expansion of mesangium.