Received for publication November 8, 2005.
Revised February 2, 2006.
Accepted for publication February 2, 2006.

Evidence for a control of plasma serotonin levels by 5-HT_2B receptors in mice

Abstract

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), wildtype mice develop lung vascular remodeling and pulmonary hypertension. We previously reported that, by contrast, the development of these hypoxia-dependent alterations is totally abolished in mice with permanent (genetic) or transient (pharmacologic) inactivation of the serotonin 5-HT_2B receptor. In the present study, we asked whether 5-HT_2B 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 wildtype mice, plasma serotonin levels and 5-HT_2B 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-HT_2B receptors, plasma serotonin levels were not modified by chronic hypoxia. We then confirmed that 5-HT_2B receptors can control plasma serotonin levels by providing in vivo evidence that an acute agonist stimulation of 5-HT_2B receptor triggers a transient increase in plasma serotonin that is serotonin transporter dependent and blocked by 5-HT_2B receptor selective antagonist or genetic abalation. Our data support the notion that a 5-HT_2B receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels.

Key words: animal model, hypoxia, plasma levels, receptor, serotonin, transporter

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