Home General Physiology and Biophysics 2014 General Physiology and Biophysics Vol.33, No.2, p.145–155, 2014

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Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

Published in English

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General Physiology and Biophysics Vol.33, No.2, p.145–155, 2014

Title: Potent cough suppression by physiologically active substance in human plasma
Author: Norio Akaike, Yushi Ito, Sachie K. Ogawa, Megumi Maeda, Masahito Wakita, Kazuo Takahama, Tetsuro Noguchi, Shintaro Kamei, Takayoshi Hamamoto, Misako Umehashi,  Hiroaki Maeda
Abstract: Human plasma contains wide variety of bioactive proteins that have proved essential in therapeutic discovery. However, many human plasma proteins remain orphans with unknown biological functions. Evidences suggest that some plasma components target the respiratory system. In the present study we adapted heparin affinity chromatography to fractionate human plasma for functional bioassay. Fractions from pooled human plasma yielded particular plasma fractions with strong cough suppressing effects. Purification yielded a fraction that was finally identified as an activated blood coagulation factor XIa (fXIa) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS). The fraction almost completely suppressed coughs induced by either chemical or mechanical stimulation applied to larynx or bifurcation of guinea-pig trachea. Cough suppressing effect of the fraction and commercially available fXIa were one million times stronger than codeine and codeine only partially suppressed the mechanically triggered coughing in animal model. Recent reviews highlighted prominent shortcomings of current available antitussives, including narcotic opioids such as codeine and their unpleasant or intolerable side effects. Therefore, safer and more effective cough suppressants would be welcome, and present findings indicate that fXIa in human plasma as a very promising, new therapeutic candidate for effective antitussive action.
Keywords: Human plasma — Cough suppressing factor — Factor XIa
Year: 2014, Volume: 33, Issue: 2 Page From: 145, Page To: 155
doi:10.4149/gpb_2013083


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