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Sixteen in vitro neurotransmitter receptor competitive bindings studies on cockle extract

Project Code: B16005

27/08/2004

1.1 Study Design

The relative binding affinities of the soluble components of two cockle extracts (positive and negative respectively for an “atypical” response in a mouse bioassay) and Tween-60 at
sixteen physiologically important rat neurotransmitter receptors, were determined in vitro using competitive radioligand binding assays.

1.2 Results

The soluble components of the cockle extract positive for the “atypical” response in the mouse bioassay displayed no binding affinity, over and above that observed with the negative
cockle extract (cockle extract negative for the “atypical” response in the mouse bioassay) and the extract vehicle (Tween-60), for fifteen of the mammalian neurotransmitter receptors
examined in this study. A component in the positive extract did display a reproducible differential affinity for the rat neuronal α₄β₂ acetylcholine nicotinic receptor that was greater
than that observed with the equivalent concentration of the negative extract or the Tween-60 vehicle. The mean IC50 value (half-maximal inhibitory concentration) for the positive cockle extract in the competitive binding assay for this receptor was a 10^-3.5 dilution of the original extract. This was a 6-fold lower concentration than the mean IC₅₀ value observed for the negative extract of a 10^-2.7 dilution of the original extract.

1.3 Conclusion

The positive cockle extract showed no binding affinity for fifteen out of the sixteen neurotransmitter receptors assayed in the present study, but did display a significantly higher
(mean 6-fold) binding affinity for the rat neuronal α₄β₂ acetylcholine nicotinic receptor when compared to the negative cockle extract. An interaction at the rat neuronal α₄β₂ acetylcholine nicotinic receptor by a soluble component of the positive cockle extract may play a role in the mechanism of action associated with the mouse bioassay “atypical” neurotoxic response induced by the positive cockle extract.

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