Yes / The Sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor
(β1AR) are G protein-coupled receptors (GPCRs) expressed in the heart. These two GPCRs have
opposing actions on adenylyl cyclase due to differential G protein-coupling. Importantly, both of
these receptors can be regulated by the actions of GPCR kinase-2 (GRK2), which triggers
desensitization and down-regulation processes. Although, classical signaling paradigms suggest
that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply be opposing action
on cAMP production, in this report we have uncovered a direct interaction between these two
receptors with a regulatory involvement of GRK2.
In HEK293 cells overexpressing both β1AR and S1PR1, we
demonstrate that β1AR down-regulation can occur after sphingosine 1-phosphate (S1PR1 agonist)
stimulation while S1PR1 down-regulation can be triggered by isoproterenol (βAR agonist)
treatment. This cross-talk between these two distinct GPCRs appears to have physiological
significance since they interact and show reciprocal regulation in mouse hearts undergoing chronic
βAR stimulation and also in a rat model of post-ischemic heart failure (HF).
We demonstrate that restoring cardiac plasma membrane levels of S1PR1
produce beneficial effects counterbalancing deleterious β1AR overstimulation in HF.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/7923 |
| Date | 09 August 2013 |
| Creators | Cannavo, A., Rengo, G., Liccardo, D., Pagano, G., Zincarelli, C., De Angelis, M.C., Puglia, R., Di Pietro, E., Rabinowitz, J.E., Barone, M.V., Cirillo, P., Trimarco, B., Palmer, Timothy M., Ferrara, N., Koch, W.J., Leosco, D., Rapacciuolo, A. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted Manuscript |
| Rights | (c) 2013 The Authors. Full-text reproduced in accordance with the publisher's self-archiving policy. |
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