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Figure 3 | BMC Systems Biology

Figure 3

From: Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation

Figure 3

Reaction 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).

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