All animal experiments were carried out according to the German Animal Welfare Act considering the guidelines of the NIH and the 2010/63/EU Directive of the European Parliament on the protection of animals used for scientific purposes. Animal experiments were done with approval by the Landesamt für Gesundheit und Soziales (Berlin) under the approval number G 0165/19. The animals had free access to food and water and were kept in individually ventilated cages under a 12-:12-h light/dark regime (light from 6:30 AM to 6:30 PM), a constant 22 °C ± 2 °C temperature, and 55 ± 10% humidity.

The transgenic lines β1-AR-TG4 and β2-AR-TG32 were generated in house and express human β1- or β2-ARs, respectively, under the control of a murine α-myosin heavy-chain promoter (5). β12–AR k.o. mice originally generated and provided by the Kobilka laboratory were obtained from The Jackson Laboratory (stock no. 003810). They are homozygous null for the adrb1 and adrb2 genes (54). For studies on endogenous β-ARs expression levels, wt littermates were used that were generated during heterozygous breeding of the β2-AR-TG32 mouse strain. Further details can be found in SI Appendix, Supplementary Materials and Methods.

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