Serotonin in the lung. Demonstration of a close correlation to blood platelet

Abstract

The dependency of a high level of serotonin (5-hydroxytryptamine, 5HT) in the lung on blood 5HT was examined. The whole lung excised from NOD/Shi mice (male, 8-12 week old) immediately after being sacrificed by cervical dislocation contained 2.86 +/- 1.21 micrograms/g of 5HT per wet tissue. This amount was much higher than that explained by the included blood which was estimated by the hemoglobin concentration in the lung extract. In order to decrease 5HT level in the blood, platelet was depleted by an exposure to gamma-ray. On the 10th day after the irradiation the amount of 5HT in the lung and blood decreased to about 3.1% and 1.5% of the respective normal values. The progressive decrease in 5HT in the lung and blood of the irradiated mice was prevented by the transplantation of normal bone marrow cells (10(7) cells/mouse). 5HT in the intestine did not change significantly. The correlation between 5HT in the excised lung and the number of platelets in the blood was statistically significant (correlation coefficient r = 0.61). The irradiated, platelet-deficient mice were incapable of accumulating serotonin in the lung, while normal mice increased the lung serotonin more than 3-fold, when high doses of 5HT were administered. The results indicated that the high level of 5HT in the dissected lung was closely related to platelet in the blood. A question remained where the majority of the measured 5HT was located in the lung tissue.

Effects of serotonin on airways: recent developments

“…Platelet aggregation is common in immunologic disease, e.g., in IgEinduced systemic anaphylaxis (15), as well as in viral (35) and bacterial (60) infections, conditions known to cause hyperreactivity even in normal persons (21). The level of 5-HT in the lung is closely related to that of platelets in the blood (122). Moreover, 5-HT released from aggregated platelets may cause bronchoconstriction manifested as wheezing in a patient with pulmonary embolism (109).…”

Cervical dislocation of mice induces rapid accumulation of platelet serotonin in the lung

“…The amount of 5HT in the lung isolated from mice after cervical dislocation varied widely (ranged from approximately 3 to 8 pg/g tissue) for unknown reasons. In a single set of experiments, however, the relative standard deviation of the measurement was about 45% with 5-7 animals as described previously [3]. The amount of 5HT in the blood was 3.12_+ 0.20 ~tg/g (mean__+S.D., n=5), and was not significantly different from that previously reported [3] (p>0.05).…”

“…We also detected a high level of 5HT in lung which was dissected from mice sacrificed by cervical dislocation, and showed that the 5HT level was closely related to the number of platelets in the blood [3]. The candidates for 5HT containing cells in lung tissue were argyrophilic endocrine cells [4,5] or neuro-epithelial bodies [6][7][8][9], macrophages [10], Abbreviations: 5HT, 5-hydroxytryptamine; PBS (--), Ca 2+ and Mg 2+ free Dulbecco's phosphate-buffered saline (33); EDTA, et hylenediaminetetraacetic acid.…”

“…Prazosin and ketanserin tartrate were donated by Daito-Pfizer Co. Ltd (Tokyo, Japan) and Janssen-Kyowa Co. Ltd. (Tokyo, Japan), respectively. Sources of other reagents were as described previously [3]. Buffers for elution of the HPLC column were filtered through a 0.45 pm filter and de-aerated before use.…”

“…After collecting 5 fractions (1 fraction: approximately 750 lal), the lung was dissected and the amount of 5HT in the tissue was measured as "residual". The hemoglobin concentration in each perfusate was measured by its absorbance at 415 nm as described previously [3]. In order to obtain a platelet-free perfusate, a 200-~tl portion was centrifuged at 8600 x g for 10 min.…”