Synaptosomal membrane functions were monitored, after in vitro exposure to select environmental pollutants, in synaptosomal preparations originating from rat cerebral cortices. The uptake of NE and 5HT into the synaptosomes was monitored as was the K+-dependent phosphate activity of the membrane. CH3HgCl, Hg(NO3)2, CdCl2, diisopropylfluorophosphate (DFP), paraoxon, acrylamide and Kepone were the test chemicals whose effects were studied.
CH3HgCl, Hg(NO3)2 and Kepone had the greatest inhibitory effects on NE and 5HT uptake. The concentrations producing 50 percent inhibition (IC50) were 1.4x10-4, 4.0x10-4, and 9.4x10-5 M, respectively, for NE uptake while the IC50's for 5HT uptake were 1.9x10-4, 6.0x10-4, and 3.3x10-4 M, respectively. Maximal inhibition was 60-100 percent at 10-3 M while the effective concentration range was between 10-4-10-3 M. The remaining test compounds produced no significant inhibition at concentrations up to 10-3 M.
K+-dependent phosphatase was strongly inhibited by CH3HgCl, Hg(NO3)2, CdCl2, and Kepone with IC50's of 1.5x10-6, 0.032x10-6, 1.5x10-6, and 13.0x10-6 M, respectively. The effective inhibitory concentrations for these chemicals ranged from 10-7-10-3 M and suggested a specific high affinity inhibition. DFP, paraoxon and acrylamide did not produce a significant inhibition at concentrations between 10-5-10-3 M.
A correlation of the phosphatase and monoamide uptake inhibitions, in search of a cause-effect relationship, was not suggested from the data. However, the low affinity inhibition (IC50 greater than 10-5 M) of the NE and 5HT uptake by CH3HgCl, Hg(NO3)2 and Kepone, along with the general shape of the dose-response curve is suggestive of an all-or-none inhibition. The apparent high affinity inhibition (IC50 less than 10-5 M) of the phosphatase demonstrates the specific influences of these compounds can have on enzymatic processes. Such enzymatic inhibition could be of critical importance if these neurotoxicants were able to penetrate the synaptosomal or even neuronal membrane and gain access to the metabolic and synthetic machinery.
| Identifer | oai:union.ndltd.org:UTAHS/oai:digitalcommons.usu.edu:etd-5212 |
| Date | 01 May 1980 |
| Creators | Bracken, William M. |
| Publisher | DigitalCommons@USU |
| Source Sets | Utah State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | All Graduate Theses and Dissertations |
| Rights | Copyright for this work is held by the author. Transmission or reproduction of materials protected by copyright beyond that allowed by fair use requires the written permission of the copyright owners. Works not in the public domain cannot be commercially exploited without permission of the copyright owner. Responsibility for any use rests exclusively with the user. For more information contact Andrew Wesolek (andrew.wesolek@usu.edu). |
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