Molecular and Cellular Analysis of Dopamine and Serotonin Transporters

Re: Presentation 147

On Thu Dec 10, Grover wrote
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>Dr. Pogun:
> Very interesting results. Do you think that the action of NO is via a guanylate cyclase or directly on the transporters due to oxidation of the transporters?

We do not think that the action of NO on the transporters is through guanylate cyclase, based on our previous in-vitro assays (unpublished). We were not able to show inhibition of uptake by cGMP in-vitro. Similarly, we have previously shown in-vitro that the action of NO is not through the binding site [Pogun, S., Baumann, M. H., Kuhar, M. J. (1994) Nitric Oxide Inhibits 3H-Dopamine uptake. Brain Res., 641: 83-91; Pogun, S., Dawson, W., Kuhar, M. J. (1994) Nitric Oxide Inhibits 3H-Glutamate Transport in Rat Synaptosomes. Synapse, 18: 21-26.]. At this point, we are not sure of the mechanism of action, therefore we cannot say that it is oxidation of the transporter either. However, it looks as if the transporter function is being reversibly modified. Further research is being carried out in our lab to elucidate this.

Tue Dec 15