The peripheral-type benzodiazepine receptor (PTBR) of trout brain was
pharmacologically characterized and pyrethroid interaction with this site
investigated. High-affinity binding sites for [³H]PK 11195 were detected in brain
membranes of rainbow trout; these shared some of the characteristics of the
PTBR of rodent brain (i.e., high affinity for PK 11195 and an endogenous ligand
protoporphyrin IX) but were unique in the low affinity for Ro5-4864. Permethrin
displaced [³H]PK 11195 binding with micromolar affinity while deltamethrin had
less than 50% efficacy at displacement. Thus the PTBR appeared not to be
relevant to pyrethroid toxicity in rainbow trout.
Pyrethroid interaction with the GABA, receptor was investigated using
[³⁵S]TBPS as a radioligand probe and by measurement of GABA-stimulated ³⁶c1-
influx in vesicle preparations. At micromolar concentrations, deltamethrin,
cypermethrin isomers and other pyrethroids inhibited [³⁵S]TBPS binding by 55-
95% with limited stereoselectivity. Pyrethroids were found to effect a GABAdependent
inhibition of [³⁵S]TBPS binding. Ro5-4864, which showed micromolar
affinity for the trout PTBR, produced a GABA-modulated interaction with
[³⁵S]TBPS binding. These results delineate the reciprocal allosteric interactions
between a pyrethroid binding site, a Ro5-4864 binding site, the GABA
recognition moiety and the TBPS binding site in trout brain. However,
pyrethroids exhibited a modest affinity for this binding site on the GABAA
receptor.
Pyrethroids indirectly inhibited the GABA-dependent influx of ³⁶Cl⁻into trout
brain synaptoneurosomes by increasing the basal uptake of chloride, thereby
compromising the ability of the vesicles to respond to applications of GABA.
This pyrethroid effect was of nanomolar potency, stereospecific, tetrodotoxinsensitive
and mimicked by veratridine. These results suggest that the primary
effect of pyrethroids in trout brain, as measured by this assay, was due to an
interaction with voltage-dependent sodium channels, increasing sodium
conductance and thereby increasing the basal uptake of ³⁶Cl⁻ through a voltagesensitive
channel.
The convulsant activity of deltamethrin was tested in rainbow trout. The
EC₅₀ for convulsant severity was 32 μg /kg body weight. By comparison,
pyrethroids at these concentrations in rodents produce no overt toxicity but act
as potent proconvulsants. / Graduation date: 1990
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/38223 |
| Date | 31 January 1990 |
| Creators | Eshleman, Amy J. |
| Contributors | Murray, Thomas F. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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