This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.To examine the effects of pyrithione on intracellular calcium concentrations in monkeys.Pyrithione (PT), administered as sodium pyrithione, and the terminal serum metabolite, 2-methylsulfonyl pyridine (2-MSP), were tested for their potential to induce an increase in intracellular calcium in motor neurons from the monkey. PT produces a sustained increase in intracellular calcium in monkey motor neurons. The EC50 for this increase is 10 M. This effect is blocked by SKF 96365, an antagonist of calcium-release-activated calcium channels. The data suggest that PT increases membrane permeability to calcium by opening a non-voltage-gated calcium ion channel. Previous investigation showed that PT also produces an increase in intracellular calcium in motor neurons from the rat, but the EC50 is 0.31 M. 2-MSP is without effect on inducing an increase in intracellular neuronal calcium in either species. PT produces neurotoxicity to the rat. This effect has not been observed in the monkey even when administered at dose levels significantly higher than that which causes the effect in rats. This investigation provides evidence for a probable biochemical mechanism that could explain the selective neurotoxicity in rats compared to monkeys following administration of PT. This research used WNPRC Animal Services.Support is from a subcontract from Yale University supported by OLIN Corporation.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000167-47A1
Application #
7716475
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2008-07-23
Project End
2009-04-30
Budget Start
2008-07-23
Budget End
2009-04-30
Support Year
47
Fiscal Year
2008
Total Cost
$40,957
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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