Invited Symposium: Molecular and Cellular Analysis of Dopamine and Serotonin Transporters
Discussion and Conclusion
Both dF and Ro4-1284 induce a rapid (within few min in our conditions) release of 5-HT from storage vesicles to the cytoplasm.
In the absence of pargyline, such an increase of cytoplasmic 5-HT is followed by:
Thus, the increased cytoplasmic 5-HT concentration is per se not sufficient to activate a carrier-mediated transport of 5-HT; but in the presence of a substrate, the carrier-mediated 5-HT release is more rapid than 5-HT metabolism.
In the presence of pargyline, RO4-1284 induced a carrier-independent [3H]5-HT release, suggesting that cytoplasmic 5-HT may cross the plasma membrane by a carrier-independent route, which is delayed as compared to the carrier-dependent way active in the presence of a carrier substrate. Such a finding had been previously described in cells (Cinquanta et al., 1996) and in slices (Reimann and Schneider, 1998). However, when allowed (in the absence of pargyline) the 5-HT metabolism appeared to be more rapid than the carrier-independent 5-HT efflux.
Some of these conclusions are at variance with those suggested by Jones et al. (1998), by studying the endogenous DA-induced release from slices. In particular they found:
It would be important to understand the reason for these discrepancies, which might be accounted for by:
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|Gobbi, M; Dalla Valle, F; Ciapparelli, C; Mennini, T; (1998). Role of the 5-HT Transporter in the Drug-Induced 'Carrier-Dependent' Release. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/simantov/gobbi0727/index.html|
|© 1998 Author(s) Hold Copyright|