Simulated effects of increased basal AC activity on β2AR-mediated cAMP signaling. (A and B)Increasing basal adenylyl cyclase activity from control levels of 0.005 μM/s to 0.05 μM/s increased both the basal PKA and PDE activities, in essence priming the negative feedback loop. The effects of this priming phenomena were (B) smaller cAMP signals leading to (A) decreased peak currents through CNG channels. In addition, the overall kinetics of the signal were slowed with increased basal AC activity, and, at the highest basal AC activity shown, were no longer transient.