Editing Platelet (section)

====Inhibition====
Factors from the lining of vessels stop platelets from activating. An intact endothelial lining ''inhibits'' platelet activation by producing [[nitric oxide]], endothelial-[[apyrase|ADPase]], and [[prostacyclin|PGI<sub>2</sub>]] (prostacyclin). Endothelial-ADPase degrades the platelet activator [[adenosine diphosphate|ADP]].{{citation needed|date=December 2021}}

Resting platelets maintain active calcium [[efflux (microbiology)|efflux]] via a [[cyclic AMP]]-activated calcium pump. Intracellular calcium concentration determines platelet activation status, as it is the [[second messenger]] that drives platelet conformational change and degranulation. Endothelial [[prostacyclin]] binds to [[prostacyclin receptor|prostanoid]] receptors on the surface of resting platelets. This event stimulates the coupled [[Gs alpha subunit|Gs]] protein to increase [[adenylate cyclase]] activity and increases the production of cAMP, further promoting the efflux of calcium and reducing intracellular calcium availability for platelet activation.{{citation needed|date=December 2021}}

ADP on the other hand binds to [[purinergic receptor]]s on the platelet surface. Since the thrombocytic purinergic receptor [[P2Y12]] is coupled to [[Gi alpha subunit|Gi]] proteins, ADP reduces platelet adenylate cyclase activity and cAMP production, leading to accumulation of calcium inside the platelet by inactivating the cAMP calcium efflux pump. The other ADP-receptor [[P2Y1]] couples to Gq that activates phospholipase C-beta 2 ([[PLCB2]]), resulting in [[inositol 1,4,5-trisphosphate]] (IP3) generation and intracellular release of more calcium. This together induces platelet activation. Endothelial ADPase degrades ADP and prevents this from happening. [[Clopidogrel]] and related antiplatelet medications also work as purinergic receptor [[P2Y12]] [[receptor antagonist|antagonists]].{{citation needed|date=December 2021}} Data suggest that ADP activates the [[PI3K/Akt]] pathway during a first wave of aggregation, leading to thrombin generation and [[protease-activated receptor 1|PAR‐1]] activation, which evokes a second wave of aggregation.<ref name="JiangXu2013">{{cite journal |last1=Jiang |first1=L. |last2=Xu |first2=C. |last3=Yu |first3=S. |last4=Liu |first4=P. |last5=Luo |first5=D. |last6=Zhou |first6=Q. |last7=Gao |first7=C. |last8=Hu |first8=H. |title=A critical role of thrombin/PAR-1 in ADP-induced platelet secretion and the second wave of aggregation |journal=Journal of Thrombosis and Haemostasis |volume=11 |issue=5 |year=2013 |pages=930–940 |issn=1538-7933 |doi=10.1111/jth.12168 |pmid=23406164 |doi-access=free}}</ref>