{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:38Z","timestamp":1792042298889,"version":"4.4.0"},"reference-count":35,"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":[[2000,10,10]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>\u2014In adult human heart, both \u03b2<jats:sub>1<\/jats:sub>- and \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of \u03b2<jats:sub>1<\/jats:sub>- and \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>\u2014Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 21\/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of \u03b2<jats:sub>1<\/jats:sub>-adrenergic receptors with (\u2212)-norepinephrine (NE) and \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors with (\u2212)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (\u2212log EC<jats:sub>50<\/jats:sub>[mol\/L] NE 5.5\u00b10.1, n=12; EPI 5.6\u00b10.1, n=13 patients), hastening of the time to reach peak force (\u2212log EC<jats:sub>50<\/jats:sub>[mol\/L] NE 5.8\u00b10.2; EPI 5.8\u00b10.2) and 50% relaxation (\u2212log EC<jats:sub>50<\/jats:sub>[mol\/L] NE 5.7\u00b10.2; EPI 5.8\u00b10.1). Ventricular membranes from Fallot infants, labeled with (\u2212)-[<jats:sup>125<\/jats:sup>I]-cyanopindolol, revealed a greater percentage of \u03b2<jats:sub>1<\/jats:sub>- (71%) than \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors (29%). Binding of (\u2212)-epinephrine to \u03b2<jats:sub>2<\/jats:sub>-receptors underwent greater GTP shifts than binding of (\u2212)-norepinephrine to \u03b2<jats:sub>1<\/jats:sub>-receptors.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014Despite their low density, \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptors are nearly as effective as \u03b2<jats:sub>1<\/jats:sub>-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G<jats:sub>s<\/jats:sub>-protein.<\/jats:p>","DOI":"10.1161\/01.cir.102.15.1814","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"1814-1821","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Both \u03b2<sub>2<\/sub>- and \u03b2<sub>1<\/sub>-Adrenergic Receptors Mediate Hastened Relaxation and Phosphorylation of Phospholamban and Troponin I in Ventricular Myocardium of Fallot Infants, Consistent With Selective Coupling of \u03b2<sub>2<\/sub>-Adrenergic Receptors to G<sub>s<\/sub>-Protein"],"prefix":"10.1161","volume":"102","author":[{"given":"Peter","family":"Molenaar","sequence":"first","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Bartel","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Cochrane","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donathe","family":"Vetter","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homayoun","family":"Jalali","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Pohlner","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie","family":"Burrell","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Karczewski","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst-Georg","family":"Krause","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Kaumann","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbru\u0308ck Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children\u2019s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.66.6.1971535"},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"Kaumann AJ Sanders L Lynham JA et al. \u03b22-Adrenoceptor activation by zinterol causes protein phosphorylation contractile effects and relaxant effects through a cAMP pathway in human atrium. Mol Cell Biochem. 1996;163\/164:113\u2013123.","DOI":"10.1007\/BF00408647"},{"key":"e_1_3_2_3_2","first-page":"889","volume":"88","year":"1993","unstructured":"DelMonte F, Kaumann AJ, Poole-Wilson PA, et al. Coexistence of functional \u03b21- and \u03b22-adrenoceptors in single myocytes from human ventricle. Circulation. 1993;88:889\u2013893.","journal-title":"Circulation"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.1.65"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Kaumann AJ Hall JA Murray JA et al. A comparison of the effects of adrenaline and noradrenaline on human heart: the role of \u03b21- and \u03b22-adrenoceptors in the stimulation of adenylate cyclase and contractile force. Eur Heart J. 1989;10(suppl B):29\u201337.","DOI":"10.1093\/eurheartj\/10.suppl_B.29"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.79.6.1059"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.76.6.1028"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.85.11.1101"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.85.11.1092"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00498852"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00165555"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0026-895X(25)11117-6","volume":"35","year":"1989","unstructured":"Bristow MR, Hershberger RE, Port JD, et al. \u03b21- and \u03b22-Adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol. 1989;35:295\u2013303.","journal-title":"Mol Pharmacol"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0026-895X(25)09146-1","volume":"41","year":"1992","unstructured":"Green SA, Holt BD, Liggett SB. \u03b21- And \u03b22-adrenergic receptors display subtype-selective coupling to Gs. Mol Pharmacol. 1992;41:889\u2013893.","journal-title":"Mol Pharmacol"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10798"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199707000-00003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00798207"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1965.20.4.755"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2660115"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31500-4"},{"key":"e_1_3_2_20_2","first-page":"215","volume":"6","year":"1995","unstructured":"Kaumann AJ, Lynham JA, Sanders L, et al. Contribution of differential efficacy to the pharmacology of human \u03b21- and \u03b22-adrenoceptors. Pharmacol Commun. 1995;6:215\u2013222.","journal-title":"Pharmacol Commun"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)92601-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113569"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.70.4.1551195"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1993.tb04709.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0026-895X(25)14062-5","volume":"17","year":"1980","unstructured":"Kent RS, DeLean A, Lefkowitz RJ. A quantitative analysis of beta-adrenergic receptor interactions: resolution of high and low affinity binding states of the receptor by computer modelling of ligand binding data. Mol Pharmacol. 1980;17:14\u201323.","journal-title":"Mol Pharmacol"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.8.4734"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050728"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.5.H1625"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/S0022-3565(24)36814-4","volume":"282","year":"1997","unstructured":"Skeberdis VA, Jurevicius J, Fischmeister R. \u03b22-Adrenergic activation of L-type Ca2+ current in cardiac myocytes. J Pharmacol Exp Ther. 1997;282:452\u2013461.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00002-9"},{"key":"e_1_3_2_31_2","first-page":"40","volume":"61","year":"1972","unstructured":"Diekmann L, Hilgenberg F. H\u00e4modynamische Untersuchungen mit Isoprenalin und \u03b2-Rezeptorenblockern bei Kindern mit Fallotscher Tetralogie. Z Kreislaufforsch. 1972;61:40\u201352.","journal-title":"Z Kreislaufforsch"},{"key":"e_1_3_2_32_2","first-page":"519","volume":"1","year":"1966","unstructured":"Cumming GR, Carr W. Relief of dyspnoeic attacks in Fallot\u2019s tetralogy with propranolol. Lancet. 1966;1:519\u2013522.","journal-title":"Lancet"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90396-I"},{"key":"e_1_3_2_34_2","first-page":"219","volume":"311","year":"1993","unstructured":"Kaumann AJ, Sanders L. Both \u03b21- and \u03b22-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human right atrium. Naunyn Schmiedebergs Arch Pharmacol. 1993;311:219\u2013236.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.6.1914"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.102.15.1814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T20:36:37Z","timestamp":1743366997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.102.15.1814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10,10]]},"references-count":35,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2000,10,10]]}},"alternative-id":["10.1161\/01.CIR.102.15.1814"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.102.15.1814","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,10,10]]},"assertion":[{"value":"2000-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-05-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}