Figure 3From: Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulationReaction scheme under basal and elevated cAMP conditions. (A) Reaction scheme for defined basal levels of the cyclic nucleotides cAMP and cGMP hold in unstimulated platelets. A constant generation of cyclic nucleotides by the corresponding cyclase (reaction r1,r2) is balanced by degradation accomplished by active phosphodiesterases PDE2, PDE3 and the cGMP-specific PDE5 (reactions r8-r13) of the cyclic nucleotides (reactions r3-r7). The explicit formulation of the underlying reactions r1 to r13 is given in the Appendix. Reaction scheme for feedback-controlled regulation of cAMP levels considering cAMP-elevating treatment (PDE3 inhibition, AC activation) thereby forcing platelet inhibition (anti-platelet effect): (B) Platelet PDE3 inhibition (competitive inhibition via Milrinone, Cilostamide). The cAMP influx (reaction r1) and cAMP degradation (reaction r2,r7) via active phosphodiesterases PDE2, PDE3 (reactions r3-r6) act as a counterbalance. (C) Activation of AC via Iloprost and Forskolin. Elevated cAMP level due to the increased cyclase activity (reaction r8) is enzymatically degraded (reaction r2,r3) mediated by active platelet PDEs (reactions r4-r7).Back to article page