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

✍ Scribed by Y.-Q. Hu; B.-J. Liu; D. E. Dluzen; Dr. P. H. Koo

• Book ID: 102911628
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 694 KB
• Volume: 43
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490430109

✦ Synopsis

Monoamine-activated alpha-2-macroglobulin (a2M) 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 a,M (MA-a,M) upon striatal dopaminergic 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 pM MA-a,M 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 pM) of MA-a,M were tested for their capacity to alter DA release. Only the 2.8 pM dose of MA-a,M was effective in producing a significant increase of DA release. In experiment 3, the normal form of a,M (N-a,M) at 2.8 pM was compared with the control superfusions. The infusion of N-a,M produced an increase in DA release which was substantially lower than the DA increase induced by MA-a,M, and not significantly different from that of the control superfusion. These results show that MA-a,M, like some other neurotoxins, can markedly alter CP dopaminergic 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.