Dynamics of platelet mobilisation into lungs in response to 5-hydroxytryptamine (serotonin) in mice.
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.
Yu
Zhiqian
Z
Department of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, Japan.
Ohba
Mami
M
Nakamura
Masanori
M
Sasano
Takashi
T
Ono
Masao
M
Sugawara
Shunji
S
Endo
Yasuo
Y
D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D006632:Histamine / Q000097:blood / Q000378:metabolism; D007275:Injections, Intravenous; D007650:Ketanserin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D010976:Platelet Count; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D000244:Adenosine Diphosphate; D005473:Fluoxetine; D006632:Histamine; D007650:Ketanserin; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors