Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo.

摘要: The type I adenylyl cyclase is directly stimulated by Ca2+ and calmodulin in vivo (Choi, E. J., Wong, S. T., Hinds, T. R. Storm, D. (1992) J. Biol. Chem. 267, 12440-12442; Wu, Z., (1993) 268, 23766-23768). In this study, we examined the sensitivity of expressed HEK-293 cells to beta-adrenergic agonists or glucagon when intracellular was elevated ionophore carbachol. Although previous studies have shown that enzyme can be activated Gs vitro, demonstrate it not Gs-coupled receptors vivo. However, Ca2+. For example, A23187 3 +/- 0.5-fold (n = 9) isoproterenol alone did stimulate enzyme, but combination two 13 2-fold Similarly, 500 nM 90 8-fold 4). Synergistic stimulation activity also obtained with combinations carbachol glucagon. This phenomenon observed a mutant insensitive calmodulin, suggesting conformational changes caused binding enhance coupling Gs. These data illustrate couple neurotransmitter signals generate optimal cAMP levels, property may important for its role learning memory mammals.