Cyclic AMP Pathway (cAMP) PDF

& (1,11-1 5S-- &D8 resting state of PIt Cyclic AMP pathway (cAMP) ’ It is a negative regulator of platelets activation. It inhibits - 1....

& (1,11-1 5S-- &D8 resting state of PIt Cyclic AMP pathway (cAMP) ’ It is a negative regulator of platelets activation. It inhibits - 1. 2. 3 ’ shape change, platelet secretion, and integrin activation & e (conversion of GPIIb/IIIa to an active form). ’ Adenyl cyclase enzyme produces cAMP. ’ ADP inhibits adenyl cyclase thus prevents cAMP production and allows platelets activation. ’ Prostacyclin from the normal endothelial cells (away from the injured site) activates adenyl cyclase to produce cAMP. This is one way to limit and localize the formation of primary hemostatic plug. Also endothelial cells have an ADPase enzyme that cleaves ADP to AMP, limiting the agonist effect of ADP.  & t.. & - - I : & Es ' S 8 & Si - -I s 88 I - Sig S - - 8 - S S S ↓· ~ - : - - = - ⑤ · - ⑤ ~ ⑰ - I - j S 1 - ⑤ E ↳ - ↳ S I # 8 &i & ⑤ : E 1 d S & i - ·⑤ - ⑮ - E ·b. Si SS: 18 S - ⑤ - - - 8 ⑤ I E.. i I. :I I &>s - T - :8 ,. - & - - &i -- j S S & - ! ⑤ - j e ⑤ # - : 8 : - - & I. -- Si 88 8, ’ - Primary messengers are extracellular signaling molecules which binds to their respective receptors on the cell surface and initiates intracellular activities within the cells. ’ -Second messengers are intracellular signaling molecules that are activated by primary messenger to target and trigger certain physiological processes. ’ cAMP is a second messenger. Prostacyclin  activated injury - &It healthy -> pH resting xA26e %constrati S - > - ’ - release of PGI2 from healthy endothelium will result in an increase in cAMP levels inside platelets inhibiting their aggregation.  Platelets and Secondary Hemostasis process Jk2, r fibrin formation () g dy coagulation factor 5-1) surface (1 PIt SI -[How - do Ifacilitate fibrin formation] procoagulantactivity of St ’ The primary hemostatic plug is relatively unstable and easily removed. Therefore, the activated platelets facilitate fibrin formation, a function - known as procoagulant activity. ’ The coagulation factors bind to the negatively charged phospholipids on the platelets membrane. And coagulation cascade begins and fibrin production occurs. ’ The resulting platelet-coagulation factor interactions result in formation of the stable secondary hemostatic plug. Fibrin forms within and around the aggregated platelets. ’ Coagulation factors do not bind to resting platelets in the circulation. In resting platelets, the negatively charged phospholipids are located in the inner leaflet of bilayer, during the activation process, they flip-flop and move to the outer leaflet. ’ Platelet factor 3 is the old name for the procoagulant activity. ’ The stabilized platelet-fibrin mass (secondary hemostatic plug) remains in place until repair of the tissue and permanent healing occurs. Then, fibrinolysis dissolves the mass. ’ - During the activation of platelets, the membrane phospholipids flip-flop, and the negatively charged phospholipids move to the outer leaflet via a Ca++activated scramblase enzyme that reverses the asymmetric distribution of phospholipids.