| dc.creator | Said, María Matilde | |
| dc.creator | Mundiña-Weilenmann, Cecilia | |
| dc.creator | Vittone, Leticia Beatriz | |
| dc.creator | Mattiazzi, Alicia Ramona | |
| dc.date | 2002-08 | |
| dc.date | 2022-10-20T18:19:40Z | |
| dc.date.accessioned | 2023-07-15T05:06:15Z | |
| dc.date.available | 2023-07-15T05:06:15Z | |
| dc.identifier | http://sedici.unlp.edu.ar/handle/10915/144219 | |
| dc.identifier | issn:0031-6768 | |
| dc.identifier | issn:1432-2013 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/7472100 | |
| dc.description | Contractility and relaxation measurements were combined with the determination of total phospholamban (PLB) phosphorylation and the immunodetection of PLB-phosphorylation sites in the intact, beating rat heart to identify the contributions of PLB phosphorylation at the Thr¹⁷ and Ser¹⁶ residues at different levels of β-adrenoceptor stimulation. Whereas with 30-300 nM isoproterenol, phosphorylation of Thr¹⁷, the Ca²⁺-calmodulin-dependent protein kinase-II (CaMKII) site and Ser¹⁶, the protein kinase A (PKA) site, contributed approximately 50% each to PLB phosphorylation, and both participated in the relaxant action of isoproterenol, at lower a level of β-adrenoceptor stimulation (isoproterenol 0.3-3 nM), both effects were exclusively due to Ser¹⁶ phosphorylation. Increasing [Ca]<sub>o</sub> at 3 nM isoproterenol, to obtain an increase in contractility comparable to that produced by 30 nM isoproterenol, significantly increased Thr¹⁷ phosphorylation and the relaxant effect produced by 3 nM isoproterenol. An increase in Thr¹⁷ phosphorylation and in the relaxant effect of 3 nM isoproterenol was also obtained by phosphatase inhibition (okadaic acid). In this case, Ser¹⁶ phosphorylation was also increased. Moreover, perfusion with 30 nM isoproterenol in the presence of the PKA inhibitor H-89 decreased phosphorylation at both PLB residues and diminished the inotropic and relaxant responses to the β-agonist. The relative contribution of Thr¹⁷ phosphorylation to the isoproterenol-induced phosphorylation of PLB and relaxation thus increased with the level of β-adrenoceptor stimulation and the consequent increase in PKA activity. The lack of Thr¹⁷ phosphorylation at low isoproterenol concentrations might therefore be attributed to a level of PKA activity insufficient to increase [Ca]<sub>i</sub> to activate the CaMKII system and/or to inhibit the phosphatase that dephosphorylates PLB. | |
| dc.description | Centro de Investigaciones Cardiovasculares | |
| dc.format | application/pdf | |
| dc.format | 801-809 | |
| dc.language | es | |
| dc.rights | http://creativecommons.org/licenses/by/4.0/ | |
| dc.rights | Creative Commons Attribution 4.0 International (CC BY 4.0) | |
| dc.subject | Medicina | |
| dc.subject | Phospholamban phosphorylation sites | |
| dc.subject | β-Adrenoceptor stimulation | |
| dc.subject | Myocardial relaxation | |
| dc.title | The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation | |
| dc.type | Articulo | |
| dc.type | Articulo | |
