CL316243 Induces Phosphatidylinositol 3,4,5-triphosphate Production in Rat Adipocytes in an Adenosine Deaminase-, Pertussis Toxin-, or Wortmannin-Sensitive Manner

Abstract

The effect of β3-adrenoceptor (β3-AR) agonists on adipocytes treated or not treated with signaling modulators has not been sufficiently elucidated. Using rat epididymal adipocytes (adipocytes) labeled with [32P]orthophosphate, we found that treatment with the selective β3-AR agonist CL316243 (CL; 1 μM) induces phosphatidylinositol (PI) 3,4,5-triphosphate (PI[3,4,5]P3) production and that this response is inhibited by adenosine deaminase (ADA, an adenosine-degrading enzyme; 2 U/ml), pertussis toxin (PTX, an inactivator of inhibitory guanine-nucleotide-binding protein; 1 μg/ml), or wortmannin (WT, a PI-kinase inhibitor; 3 μM). The results showed that CL induced PI(3,4,5)P3 production in intact adipocytes and that this production was affected by signaling modulators. Taken together, our findings indicate that CL produces PI(3,4,5)P3 in an ADA-sensitive, PTX-sensitive, or WT-sensitive manner and will advance understanding of the effect of β3-AR agonists on adipocytes.