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Pharmacological profiling of the hemodynamic effects of cannabinoid ligands: a combined in vitro and in vivo approach.

Walsh, Sarah K.; Hepburn, Claire Y.; Keown, Oliver; �strand, Annika; Lindblom, Anna; Ryberg, Erik; Hjorth, Stephan; Leslie, Stephan J.; Greasley, Peter J.; Wainwright, Cherry L.


Claire Y. Hepburn

Oliver Keown

Annika �strand

Anna Lindblom

Erik Ryberg

Stephan Hjorth

Stephan J. Leslie

Peter J. Greasley


The receptors mediating the hemodynamic responses to cannabinoids are not clearly defined due to the multifarious pharmacology of many commonly used cannabinoid ligands. While both CB1 and TRPV1 receptors are implicated, G protein-coupled receptor 55 (GPR55) may also mediate some of the hemodynamic effects of several atypical cannabinoid ligands. The present studies attempted to unravel the pharmacology underlying the in vivo hemodynamic responses to ACEA (CB1 agonist), O-1602 (GPR55 agonist), AM251 (CB1 antagonist), and cannabidiol (CBD; GPR55 antagonist). Agonist and antagonist profiles of each ligand were determined by ligand-induced GTPcS binding in membrane preparations expressing rat and mouse CB1 and GPR55 receptors. Blood pressure responses to ACEA and O-1602 were recorded in anesthetized and conscious mice (wild type, CB1 / and GPR55 / ) and rats in the absence and presence of AM251 and CBD. ACEA demonstrated GTPcS activation at both receptors, while O-1602 only activated GPR55. AM251 exhibited antagonist activity at CB1 and agonist activity at GPR55, while CBD demonstrated selective antagonist activity at GPR55. The depressor response to ACEA was blocked by AM251 and attenuated by CBD, while O-1602 did not induce a depressor response. AM251 caused a depressor response that was absent in GPR55 / mice but enhanced by CBD, while CBD caused a small vasodepressor response that persisted in GPR55 / mice. Our findings show that assessment of the pharmacological profile of receptor activation by cannabinoid ligands in in vitro studies alongside in vivo functional studies is essential to understand the role of cannabinoids in hemodynamic control.


WALSH, S.K., HEPBURN, C.Y., KEOWN, O., ÅSTRAND, A., LINDBLOM, A., RYBERG, E., HJORTH, S., LESLIE, S. J., GREASLEY, P.J. and WAINWRIGHT, C.L. 2015. Pharmacological profiling of the hemodynamic effects of cannabinoid ligands: a combined in vitro and in vivo approach. Pharmacology research and perspectives [online], 3(3), e00143. Available from:

Journal Article Type Article
Acceptance Date Mar 14, 2015
Online Publication Date May 8, 2015
Publication Date Jun 30, 2015
Deposit Date Jul 9, 2015
Publicly Available Date Jul 9, 2015
Journal Pharmacology research and perspectives
Electronic ISSN 2052-1707
Publisher Wiley Open Access
Peer Reviewed Peer Reviewed
Volume 3
Issue 3
Article Number e00143
Keywords Cannabinoids; CB Receptor G protein coupled receptor 55; Haemodynamics
Public URL


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