Pharmacological profiling of the molecular mechanisms underlying transient isoproterenol-induced cAMP signals. Responses were elicited by exposure of CNG channel–expressing cells to 1 μM isoproterenol. (A) The decline in the cAMP transients was abolished when 10 μM rolipram (a PDE4 inhibitor) was included in the patch pipette. The decline in the response remained largely intact when 20 nM PKI (a PKA inhibitor, B) or 10 μM St-Ht31 (an AKAP-PKA disruptor, C) were included in the patch pipette, indicating the PKA was not solely responsible for the decline in the signal. (D) An 18–24-h pretreatment with PTX (an inhibitor of G_i) had little effect on the overall kinetics of the signal. (E) 3 μM 59-74E (a GRK inhibitor) did not prevent the decline in the cAMP transients. However, the decline in the response was largely eliminated when both PKI and 59-74E (F) or St-Ht31 and 59-74E (G) were included in the patch pipette. (H) Data were quantified by measuring the percentage of current remaining 3 min after the peak current.