This paper came out in Science recently, but I didn't pay much attention until it came up in a pubmed search for "hallucinogen." Then I took a closer look and…well…maybe there's more than just a CNS basis for the healing effects of hallucinogens on alcoholics…
Platelet-Derived Serotonin Mediates Liver Regeneration
Mickael Lesurtel,1 Rolf Graf,1 Boris Aleil,3 Diego J. Walther,4 Yinghua Tian,1 Wolfram Jochum,2 Christian Gachet,3 Michael Bader,5 Pierre-Alain Clavien1*
Abstract
The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.
1 Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.
2 Department of Pathology, University Hospital of Zurich, Switzerland.
3 Institut National de la Santé et de la Recherche Médicale 311, Etablissement Français du Sang-Alsace, Strasbourg, France.
4 Max Planck Institute for Molecular Genetics, Berlin, Germany.
5 Max Delbrück Center for Molecular Medicine, Berlin, Germany.
* To whom correspondence should be addressed. E-mail: [email protected]
……
Platelets store and release serotonin. About 95% of all serotonin found in blood is stored in platelets. In vitro, serotonin is a potent mitogen and stimulates hepatocyte mitosis [3, 16]. The 5-HT2A and 1C receptors appear to mediate mitogenic effects in fibroblasts [17, 18], and the 5-HT2B receptor is involved in the development of the heart [19] and the enteric nervous system [20]. To test whether serotonin induces hepatocyte proliferation in vivo, thrombocytopenic mice were treated with the serotonin receptor 5-HT2A/2C agonist [±]-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane [DOI-hydrochloride]. The application of this drug had no effect on the extent of thrombocytopenia [Fig. 2G] induced by concurrent treatment with the antibody to GPIb{alpha}. In the presence of the serotonin agonist, proliferation was completely restored [Fig. 2, D to F].
Platelet-Derived Serotonin Mediates Liver Regeneration
Mickael Lesurtel,1 Rolf Graf,1 Boris Aleil,3 Diego J. Walther,4 Yinghua Tian,1 Wolfram Jochum,2 Christian Gachet,3 Michael Bader,5 Pierre-Alain Clavien1*
Abstract
The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.
1 Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.
2 Department of Pathology, University Hospital of Zurich, Switzerland.
3 Institut National de la Santé et de la Recherche Médicale 311, Etablissement Français du Sang-Alsace, Strasbourg, France.
4 Max Planck Institute for Molecular Genetics, Berlin, Germany.
5 Max Delbrück Center for Molecular Medicine, Berlin, Germany.
* To whom correspondence should be addressed. E-mail: [email protected]
……
Platelets store and release serotonin. About 95% of all serotonin found in blood is stored in platelets. In vitro, serotonin is a potent mitogen and stimulates hepatocyte mitosis [3, 16]. The 5-HT2A and 1C receptors appear to mediate mitogenic effects in fibroblasts [17, 18], and the 5-HT2B receptor is involved in the development of the heart [19] and the enteric nervous system [20]. To test whether serotonin induces hepatocyte proliferation in vivo, thrombocytopenic mice were treated with the serotonin receptor 5-HT2A/2C agonist [±]-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane [DOI-hydrochloride]. The application of this drug had no effect on the extent of thrombocytopenia [Fig. 2G] induced by concurrent treatment with the antibody to GPIb{alpha}. In the presence of the serotonin agonist, proliferation was completely restored [Fig. 2, D to F].
