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You are here: Contents > 2014 > Volume 23 Number 2 March 2014 > MISCELLANEOUS > Function and Expression Differences Between Ergot and Non-Ergot Dopamine D2 Agonists on Heart Valve Interstitial Cells

Function and Expression Differences Between Ergot and Non-Ergot Dopamine D2 Agonists on Heart Valve Interstitial Cells

Fumiki Oana, Hiroshi Onozuka, Akihiro Tsuchioka, Takayuki Suzuki, Nobuyuki Tanaka, Kouichi Kaidoh, Yuji Hoyano, Masahiro Hiratochi, Shinji Kikuchi, Yasuo Takehana, Nobuo Shibata

Division of Discovery Research, Kissei Pharmaceutical Co., Ltd., Nagano, Japan

Background and aim of the study: The symptoms of Parkinson’s disease are alleviated by dopamine D2 agonists, which are classified as ergot dopamine D2 agonists and non-ergot D2 agonists. Among the former, pergolide has been associated with valvular heart disease, since it has both potent D2 receptor and serotonin 5-HT2B receptor agonistic properties. Among the latter, pramipexole has few incidences of heart valve disease onset, since it has an absence of 5-HT2B receptor agonism.

Method: A [3H]thymidine incorporation assay was performed to monitor function, and microarray global analysis to monitor gene expression, on porcine heart valve interstitial cells (VICs) treated with pergolide or pramipexole.

Results: The 5-HT2B receptor was abundantly expressed in porcine VICs. The 5-HT2B receptor agonist pergolide

induced an increase in [3H]thymidine incorporation, accompanied by a decrease in 5-HT2B receptor mRNA expression. [3H]thymidine incorporation was blocked by lisuride, a 5-HT2B receptor antagonist, and also by LY-294002, a specific inhibitor of PI3K and Akt. Moreover, type 2 iodothyronine deiodinase (Dio2) expression in porcine VICs treated with pergolide was shown, by a global analysis of mRNA, to be markedly increased compared to that induced by pramipexole. Such changes in VICs may correlate with the mechanism of heart valve disease pathogenesis.

Conclusion: There were substantial differences (increased [3H]thymidine incorporation, and Dio2 expression) between pergolide and pramipexole, which might correlate with the mechanism of heart valve disease onset.

The Journal of Heart Valve Disease 2014;23:246-252

Function and Expression Differences Between Ergot and Non-Ergot Dopamine D2 Agonists on Heart Valve Interstitial Cells

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