Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.
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.
Matondo
Ramadhan B
RB
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3508 TD Utrecht, The Netherlands.
Punt
Carine
C
Homberg
Judith
J
Toussaint
Mathilda J M
MJ
Kisjes
Ronald
R
Korporaal
Suzanne J A
SJ
Akkerman
Jan Willem N
JW
Cuppen
Edwin
E
de Bruin
Alain
A
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D017353:Gene Deletion; D006498:Hepatectomy; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D008115:Liver Regeneration / Q000235:genetics* / Q000502:physiology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin