Sphingosine 1-phosphate induces sinus tachycardia and coronary vasoconstriction in the canine heart.
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 beta- and alpha-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.
Sugiyama
A
A
Department of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Yamanashi, Japan. atsushisj@res.yamanashi-med.ac.jp
Yatomi
Y
Y
Ozaki
Y
Y
Hashimoto
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D008246:Lysophospholipids; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D015290:Second Messenger Systems; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013616:Tachycardia, Sinus / Q000139:chemically induced*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D001262:Atenolol; D000262:Adenylyl Cyclases; D013110:Sphingosine; D011224:Prazosin