Submitted on December 19, 2008
Revised on January 26, 2009
Accepted on February 16, 2009
Deletion of the Serotonin Transporter in Rats Disturbs Serotonin Homeostasis Without Impairing Liver Regeneration
Ramadhan B. Matondo, Carine Punt, Judith Homberg1, Mathilda J.M. Toussaint, Ronald Kisjes, Suzanne J.A. Korporaal, Jan Willem N. Akkerman, Edwin Cuppen2, and Alain de Bruin3*
1 Donders Institute for Brain, Cognition and Behaviour
2 Netherlands Institute for Developmental Biology
3 Utrecht University
* To whom correspondence should be addressed. E-mail: a.debruin{at}uu.nl.
The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver regeneration after partial hepatectomy. We have recently generated serotonin transporter knockout rats and demonstrated that their platelets were almost completely depleted of serotonin. Here we show that these rats exhibit impaired hemostasis and contain about 1-6% of wild-type serotonin levels in the blood. Despite the marked reduction of serotonin levels in blood and platelets, efficient liver regeneration and collagen-induced platelet aggregation occur in rats lacking the serotonin transporter. These results provide evidence that liver regeneration is not dependent on the release of serotonin from platelets. Our findings indicate that very low levels of serotonin in blood are sufficient for liver regeneration.
