© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Sphingosine 1-phosphate induces sinus tachycardia and coronary vasoconstriction in the canine heart
aDepartment of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan
bDepartment of Laboratory Medicine, Yamanashi Medical University, Yamanashi, Japan
* Corresponding author. Tel.: +81-55-273-9504; fax: +81-55-273-6739 atsushis{at}res.yamanashi-med.ac.jp
Objective: Sphingosine 1-phosphate is a naturally occurring biologically active lysophospholipid. Recent studies suggested that sphingosine 1-phosphate is released into the blood flow from activated platelets upon stimulation to exert multiple biological phenomenon. The purpose of this study was to assess the effects of sphingosine 1-phosphate on sinus automaticity, ventricular contraction and coronary blood flow. Methods: The canine isolated, blood-perfused sinoatrial node and papillary muscle preparations were used. Results: Sphingosine 1-phosphate increased the sinoatrial rate, while it decreased the coronary blood flow, which was followed by a weak negative inotropic effect. These positive chronotropic and coronary vasoconstrictor effects were not attenuated by the β- and 
-adrenoceptor antagonists atenolol and prazosin, respectively. Furthermore, sphingosine 1-phosphate did not affect the adenylate cyclase activity of the membrane preparations made from the canine right atrium and right ventricle, indicating the involvement of a novel signaling pathway in sphingosine 1-phosphate-induced cardiac effects. Conclusions: These results may provide a clue to better understanding the physiological as well as the pathophysiological regulation of sphingosine 1-phosphate in the heart.
KEYWORDS Lipid metabolism; Platelets; Second messengers; Sinus node; Vasoconstriction/dilation; Signal transduction
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