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. 2022 Sep 14;20:143. doi: 10.1186/s12964-022-00947-8

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Phosphodiesterases restrict β₂AR signaling at the RyR2 and SERCA2 nanodomains in AVMs. Rat AVMs expressing Cyto-AKAR3, FKBP-AKAR3, and SR-AKAR3 were treated with drugs as indicated. A and B Time courses show changes in YFP/CFP ratio of Cyto-AKAR3 in rat AVMs induced by ISO (100 nmol/L) after 5 min pretreatment of β₁AR antagonist CGP (300 nmol/L) and β₂AR antagonist ICI (100 nmol/L). The maximal changes in FRET ratio after drug treatment were plotted. C–E Time courses show changes in YFP/CFP ratio of FKBP-AKAR3 induced by ISO (100 nmol/L) after 5 min pretreatment with β₁AR antagonist CGP (300 nmol/L), which was then followed with addition of inhibitor of PDE4 (Roli, 100 nmol/L and 1 µmol/L) and PDE3 (Cilo, 1 and 10 µmol/L) as indicated. The maximal changes in FRET ratio after drug treatment were plotted. F–H Time courses show changes in YFP/CFP ratio of SR-AKAR3 induced by ISO (100 nmol/L) after 5 min pretreatment with β₁AR antagonist CGP (300 nmol/L), which was then followed with addition of inhibitor of PDE4 (Roli, 100 nmol and 1 µmol/L) and PDE3 (Cilo, 1 and 10 µmol/L) as indicated. The maximal changes in FRET ratio after drug treatment were plotted. Dot plots represent mean ± SEM of indicated number of AVMs from rats. p values were obtained by one-way ANOVA analysis followed with Tukey’s multiple comparison test