The βAR‐PI3K signaling pathway crosstalk in vivo : differential effects on downstream cascades during cardiac development

β‐adrenergic receptors (βAR) mediate many heart functions. In early cardiac development βAR and its' ligands can be detected with no activation‐contraction coupling. In adult mice chronic βAR activation leads to cardiac hypertrophy. We have shown PI3K activities are highly regulated during cardiac development and there is a βAR and PI3K crosstalk in vitro . To elucidate the signaling cascades induced by such crosstalk during cardiac development, newborn or adult mice were injected (ip) with propranolol (10 mg/kg) or isoproterenol (1.25 mg/kg), respectively, for 30min. In newborn βAR blockade induced significant decreases in PI3K activity and phosphorylation of Akt, Glycogen synthase kinase‐3α/β (GSK‐3α/β), but a paradoxical effect on phosphorylation of p70S6 kinase and FoxO1/3a (Forkhead family of transcription factors) at different sites. βAR stimulation in adults induced significant increases in PI3K activity and phosphorylation of Akt, GSK‐3α/β, mTOR, p70S6K, S6 ribosomal protein, and FoxO1/3a. There was also an increase in Erk1/2 phosphorylation. These data provide evidence for developmental regulation of the crosstalk between the βAR and PI3K pathways in mouse heart. We speculate the differential effects on the downstream cascades between newborn and adult may underline the distinct functional regulation on cellular proliferation or growth at different developing stages. (NIH 1 P20 RR018728)