Alterations of dopamine release by rat caudate putamen tissues superfused with α2-Macroglobulin

Authors

  • Y.-Q. Hu,

    1. Department of Microbiology and Immunology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
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  • B.-J. Liu,

    1. Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
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  • D. E. Dluzen,

    1. Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
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  • Dr. P. H. Koo

    Corresponding author
    1. Department of Microbiology and Immunology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
    • Department of Microbiology and Immunology, Northeastern Ohio Universities College of Medicine, P.O. Box 95, Rootstown, OH 44272
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Abstract

Monoamine-activated alpha-2-macroglobulin (α2M) has been shown to decrease the dopamine concentrations in rat caudate putamen (CP) in vivo as well as inhibit choline acetyltransferase activities in the culture of basal forebrain neurons. In this study, we further investigated the effects of methylamine-activated α2M (MA-α2M) upon striatal rlopaminergic function by determining whether a direct infusion of this glycoprotein will alter dopamine (DA) release in vitro from superfused CP tissue fragments. In experiment 1, an infusion of 2.8 μM MA-α2M produced a statistically significant increase in DA release compared with control superfusions. In experiment 2, varying doses (0, 0.7, 1.4, 2.8, 4.1 μM) of MA-α2M were tested for their capacity to alter DA release. Only the 2.8 μM dose of MA-α2M was effective in producing a significant increase of DA release. In experiment 3, the normal form of α2M (N-α2M) at 2.8 μM was compared with the control superfusions. The infusion of N-α2M produced an increase in DA release which was substantially lower than the DA increase induced by MA-α2M, and not significantly different from that of the control superfusion. These results show that MA-α2M, like some other neurotoxins, can markedly alter CP dapaminergic function as indicated by the acute increase in DA release following infusion of this glycoprotein, and these effects are exerted at a relatively narrow range of doses. Taken together, these data suggest that this glycoprotein, if allowed to accumulate in the central nervous system (CNS), may promote some neurodegenerative changes that can occur in disorders like Parkinson's disease. © 1996 Wiley-Liss, Inc.

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