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Am J Physiol Gastrointest Liver Physiol 296: G963-G968, 2009. First published February 26, 2009; doi:10.1152/ajpgi.90709.2008
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LIVER AND BILIARY TRACT

Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

Ramadhan B. Matondo,1 Carine Punt,1 Judith Homberg,2 Mathilda J. M. Toussaint,1 Ronald Kisjes,1 Suzanne J. A. Korporaal,3 Jan Willem N. Akkerman,3 Edwin Cuppen,2 and Alain de Bruin1

1Department of Pathobiology, Faculty of Veterinary Medicine, 2Hubrecht Institute, Royal Academy of Arts and Sciences and University Medical Center, and 3Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

Submitted 19 December 2008 ; accepted in final form 16 February 2009

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.

platelet; aggregation; bleeding; hepatectomy; knockout


Address for reprint requests and other correspondence: A. de Bruin, Dept. of Pathobiology, Faculty of Veterinary Medicine, Utrecht Univ., Yalelaan 1, 3508 TD Utrecht, The Netherlands (e-mail: A.debruin{at}uu.nl)






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