{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:57:16Z","timestamp":1789541836462,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,10,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>\n                      The sphingosine-1-phosphate receptor 1 (S1PR1) and \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      -adrenergic receptor (\u03b21AR) are G-protein\u2013coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein\u2013coupled receptor kinase-2, which triggers desensitization and downregulation processes. Although classic signaling paradigms suggest that simultaneous activation of \u03b21ARs and S1PR1s in a myocyte would simply result in opposing action on cAMP production, in this report we have uncovered a direct interaction between these 2 receptors, with regulatory involvement of G-protein\u2013coupled receptor kinase-2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>In HEK (human embryonic kidney) 293 cells overexpressing both \u03b21AR and S1PR1, we demonstrated that \u03b21AR downregulation can occur after stimulation with sphingosine-1-phosphate (an S1PR1 agonist), whereas S1PR1 downregulation can be triggered by isoproterenol (a \u03b2-adrenergic receptor agonist) treatment. This cross talk between these 2 distinct G-protein\u2013coupled receptors appears to have physiological significance, because they interact and show reciprocal regulation in mouse hearts undergoing chronic \u03b2-adrenergic receptor stimulation and in a rat model of postischemic heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>We demonstrate that restoration of cardiac plasma membrane levels of S1PR1 produces beneficial effects that counterbalance the deleterious \u03b21AR overstimulation in heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.113.002659","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T23:20:20Z","timestamp":1377213620000},"page":"1612-1622","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["\u03b2\n                    <sub>1<\/sub>\n                    -Adrenergic Receptor and Sphingosine-1-Phosphate Receptor 1 (S1PR1) Reciprocal Downregulation Influences Cardiac Hypertrophic Response and Progression to Heart Failure"],"prefix":"10.1161","volume":"128","author":[{"given":"Alessandro","family":"Cannavo","sequence":"first","affiliation":[{"name":"From the Division of Geriatrics, Department of Translational Medical Sciences (A.C., G.R., D.L., G.P., N.F., D.L.), Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases (M.V.B.), and Division of Cardiology, Department of Advanced Biomedical Sciences (M.C.D.A., R.P., E.D.P., P.C., B.T., A.R.), Federico II University, Naples, Italy; Center of Translational Medicine, Temple University, Philadelphia, PA (A.C., J.E.R., W.J.K.); Division of Cardiology, Salvatore..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Rengo","sequence":"additional","affiliation":[{"name":"From the Division of Geriatrics, Department of Translational Medical Sciences (A.C., G.R., D.L., G.P., N.F., D.L.), Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases (M.V.B.), and Division of Cardiology, Department of Advanced Biomedical Sciences (M.C.D.A., R.P., E.D.P., P.C., B.T., A.R.), Federico II University, Naples, Italy; Center of Translational Medicine, Temple University, Philadelphia, PA (A.C., J.E.R., W.J.K.); Division of Cardiology, Salvatore..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Liccardo","sequence":"additional","affiliation":[{"name":"From the Division of Geriatrics, Department of Translational Medical Sciences (A.C., G.R., D.L., G.P., N.F., D.L.), Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases (M.V.B.), and Division of Cardiology, Department of Advanced Biomedical Sciences (M.C.D.A., R.P., E.D.P., P.C., B.T., A.R.), Federico II University, Naples, Italy; 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