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      Effect of Morphine on Renomedullary Interstitial Cell Proliferation and Matrix Accumulation

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          Renal interstitial scarring is an important feature of heroin-associated nephropathy. We studied the effect of morphine, an active metabolite of heroin, on cultured rat renal medullary interstitial cell (RMIC) proliferation and matrix accumulation. Morphine (10<sup>-12</sup> M) enhanced (p < 0.001) the proliferation of RMIC (control, 15.0 ± 0.5 vs. morphine, 20.4 ± 1.1 × 10<sup>4</sup> cells/ml). This effect of morphine was dose and time dependent. [<sup>3</sup>H]thymidine and bromodeoxyuridine incorporation studies confirmed the mitogenic effect of morphine on RMIC. Morphine also enhanced mRNA expression for c-jun and c-myc on RMIC. However, nalbuphine, a non-addicting alkaloid did not modulate the proliferation of RMIC. Morphine enhanced the accumulation of collagen type I in a dose-dependent manner and also increased (p < 0.001) the accumulation of collagen type III at a high concentration (control, 1,291 ± 55.8 vs. morphine, 10<sup>-4</sup> M, 2,697.6 ± 257.8 ng/μg protein). Morphine did not modulate the accumulation of laminin or fibronectin. Neutralizing antibody to IL·6 inhibited the effect of morphine on RMIC. H7, a protein kinase C inhibitor, also attenuated the morphine-induced RMIC proliferation. The present study provides a basis for a hypothesis that morphine may be playing a role in the development of renal interstitial pathology in patients with heroin addiction.

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          Author and article information

          S. Karger AG
          23 December 2008
          : 77
          : 2
          : 225-234
          Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y., and The Long Island Campus for Albert Einstein College of Medicine, Bronx, N.Y., USA
          190277 Nephron 1997;77:225–234
          © 1997 S. Karger AG, Basel

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          Pages: 10
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