Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery

Mair, K.M., Robinson, E., Kane, K.A., Pyne, S., Brett, R.R., Pyne, N.J. and Kennedy, S. (2010) Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery. British Journal of Pharmacology, 161(1), pp. 176-192. (doi: 10.1111/j.1476-5381.2010.00878.x)

Abstract

<b>BACKGROUND AND PURPOSE</b> Anandamide and sphingosine-1-phosphate (S1P) both regulate vascular tone in a variety of vessels. This study aimed to examine the mechanisms involved in the regulation of coronary vascular tone by anandamide and S1P, and to determine whether any functional interaction occurs between these receptor systems. <br></br> <b>EXPERIMENTAL APPROACH</b> Mechanisms used by anandamide and S1P to regulate rat coronary artery (CA) reactivity were investigated using wire myography. Interactions between S1P and the cannabinoid (CB)2 receptor were determined using human embryonic kidney 293 (HEK293) cells that stably over-express recombinant CB2 receptor. <br></br> <b>KEY RESULTS</b> Anandamide and S1P induced relaxation of the rat CA. CB2 receptor antagonists attenuated anandamide-induced relaxation, while S1P-mediated relaxation was dependent on the vascular endothelium and S1P3. Anandamide treatment resulted in an increase in the phosphorylation of sphingosine kinase-1 within the CA. Conversely, anandamide-mediated relaxation was attenuated by inhibition of sphingosine kinase. Moreover, S1P3, specifically within the vascular endothelium, was required for anandamide-mediated vasorelaxation. In addition to this, S1P-mediated relaxation was also reduced by CB2 receptor antagonists and sphingosine kinase inhibition. Further evidence that S1P functionally interacts with the CB2 receptor was also observed in HEK293 cells over-expressing the CB2 receptor. <br></br> <b>CONCLUSIONS AND IMPLICATIONS</b> In the vascular endothelium of rat CA, anandamide induces relaxation via a mechanism requiring sphingosine kinase-1 and S1P/S1P3. In addition, we report that S1P may exert some of its effects via a CB2 receptor- and sphingosine kinase-dependent mechanism, where subsequently formed S1P may have privileged access to S1P3 to induce vascular relaxation.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kennedy, Professor Simon and Mair, Dr Kirsty
• Authors: Mair, K.M., Robinson, E., Kane, K.A., Pyne, S., Brett, R.R., Pyne, N.J., and Kennedy, S.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: British Journal of Pharmacology
• Publisher: Wiley-Blackwell
• ISSN: 1476-5381
• Copyright Holders: Copyright © 2010 The Authors
• First Published: First published in British Journal of Pharmacology 161(1):176-192
• Publisher Policy: Reproduced with permission of the author