PT - JOURNAL ARTICLE AU - J. Callebert AU - J. M. Esteve AU - P. Hervé AU - K. Peoc'h AU - C. Tournois AU - L. Drouet AU - J. M. Launay AU - L. Maroteaux TI - Evidence for a Control of Plasma Serotonin Levels by 5-Hydroxytryptamine<sub>2B</sub> Receptors in Mice AID - 10.1124/jpet.105.098269 DP - 2006 May 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 724--731 VI - 317 IP - 2 4099 - http://jpet.aspetjournals.org/content/317/2/724.short 4100 - http://jpet.aspetjournals.org/content/317/2/724.full SO - J Pharmacol Exp Ther2006 May 01; 317 AB - A correlation between high plasma serotonin levels and total pulmonary resistance was reported in more than 80% of pulmonary hypertensive patients. When submitted to chronic hypoxia (10% O2 for more than 3 weeks), wild-type mice develop lung vascular remodeling and pulmonary hypertension. We previously reported that, in contrast, the development of these hypoxia-dependent alterations is totally abolished in mice with permanent (genetic) or transient (pharmacologic) inactivation of the serotonin 5-hydroxytryptamine (5-HT)2B receptor. In the present study, we asked whether 5-HT2B receptors could be involved in the control of plasma serotonin levels. Further investigating the chronic hypoxic mouse model of pulmonary hypertension, we first show that in wild-type mice, plasma serotonin levels and 5-HT2B receptors expression were significantly increased after chronic exposure to hypoxia. This increase appeared before significant changes in remodeling factors could be detected and persisted when the pathology was established. Conversely, in mice with either genetically or pharmacologically inactive 5-HT2B receptors, plasma serotonin levels were not modified by chronic hypoxia. We then confirmed that 5-HT2B receptors can control plasma serotonin levels by providing in vivo evidence that an acute agonist stimulation of 5-HT2B receptor triggers a transient increase in plasma serotonin that is serotonin transporter dependent and blocked by 5-HT2B receptor-selective antagonist or genetic ablation. Our data support the notion that a 5-HT2B receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels. The American Society for Pharmacology and Experimental Therapeutics