Dynamics of platelet mobilisation into lungs in response to 5-hydroxytryptamine (serotonin) in mice

Abstract

In experimental animals, the lung rapidly removes intravenously injected 5-hydroxytryptamine (5HT), but the mechanism underlying this pulmonary 5HT removal (P-5HT-R) and the responsible cells remains unclear. 5HT reportedly induces rapid pulmonary platelet accumulation (P-PLT-A). Here, we examined the relationship between P-5HT-R and P-PLT-A in mice by comparing the platelet count in the blood with the endogenous 5HT in the tissues (a marker for platelets because the 5HT is largely contained within platelets). 5HT levels in murine blood and tissues were also examined after intravenous injection of 5HT. The data revealed that: (i) 5HT injection (at > or = 0.04 micromol/kg) induced a transient P-PLT-A (occurring within 6 seconds), (ii) platelets rapidly took up injected 5HT, (iii) the P-5HT-R was saturated following injection of 5HT at 1 micromol/kg, (iv) ketanserin (5HT(2)-receptor antagonist) strongly inhibited P-PLT-A, (v) under fluoxetine (5HT-uptake inhibitor), 5HT levels at 6 seconds after 5HT injection were markedly higher in blood, but significantly lower in lung (versus fluoxetine-untreated mice), (vi) P-5HT-R was barely detectable in mutant mice with platelets lacking dense bodies, and was much reduced in platelet-depleted mice, (vii) 5HT injected intravenously at 10 micromol/kg had a half-life in the lung of < 20 seconds, and (viii) unlike 5HT, injected histamine was largely excreted by the kidney. These results demonstrate that platelets rapidly translocate into the lung upon stimulation of 5HT(2) receptors, take up 5HT (and possibly swiftly metabolise it), and then return to the circulation. Hence, pulmonary platelet accumulation plays an important role in pulmonary 5HT removal in mice.

Serotonin and Cardiovascular Diseases

“…In fact, platelets rapidly translocate into lung upon stimulation of 5-HT2 receptors, take up serotonin, and then return to circulation. Hence, pulmonary platelet accumulation plays an important role in pulmonary serotonin removal in mice (Yu, et al, 2009). Ablation of the peripheral tryptophan hydroxylase 1 (Tph1) gene in mice results in a significant reduction in peripheral, essentially blood serotonin.…”

Dynamics of Platelet Behaviors as Defenders and Guardians: Accumulations in Liver, Lung, and Spleen in Mice

“…In the 1980 s, by monitoring 111 Inlabeled platelets in anesthetized guinea pigs and rats, ADP, collagen, PAF, or 5HT were found to induce PPA which, in the case of the ADP-or 5HT-induced PPA, was transient, although anesthesia was supposed to interfere with such platelet behaviors. 137,138) These observations led us to examine the effects of i.v. injected 5HT on platelets in non-anaesthetized BALB/c mice.…”

Hypertension artérielle pulmonaire, moelle osseuse, précurseurs endothéliaux et sérotonine

“…Chez la souris éveillée, une translocation rapide des plaquettes dans les poumons est induite par la stimulation des récepteurs 5-HT 2 . Les plaquettes s'accumulent dans les poumons dans les 6 secondes suivant une injection de sérotonine ou d'ADP, chez la souris (Yu et al, 2009). Ainsi, la translocation des plaquettes dans les poumons et la recapture de sérotonine par des plaquettes peuvent se produire presque immédiatement après l'injection de sérotonine.…”

“…rencontre aussi les premiers capillaires. Ainsi, il est probable que cette sérotonine puisse activer les plaquettes déjà présentes dans les poumons, mais aussi recruter les plaquettes circulantes, ce qui conduirait à l'accumulation de plaquettes dans le parenchyme pulmonaire (Yu et al, 2009). Par conséquent, l'accumulation pulmonaire des plaquettes joue un rôle important dans leur charge en sérotonine et dans l'élimination pulmonaire de la sérotonine, au moins chez la souris, et peut représenter l'un des mécanismes de protection de l'organisme contre la sérotonine.…”