Prostacyclin receptor (PTGIR) (PTGIR)

The prostacyclin receptor (PTGIR), also known as the IP receptor, is a G protein-coupled receptor (GPCR) that serves as the primary mediator for prostacyclin (PGI2) signaling [UniProt P43119]. It is predominantly expressed in vascular smooth muscle cells and platelets, where its activation leads to the stimulation of adenylate cyclase and a subsequent increase in intracellular cyclic AMP (cAMP) [NCBI Gene 5739]. This signaling cascade results in potent vasodilation and the inhibition of platelet aggregation, making it a vital component of cardiovascular homeostasis [PubMed PMID: 15123940]. In the context of disease, PTGIR is a validated therapeutic target for pulmonary arterial hypertension (PAH), a condition characterized by restricted blood flow through the pulmonary arteries and increased pulmonary vascular resistance [StatPearls: Pulmonary Hypertension]. Drugs targeting this receptor, including prostacyclin analogues like epoprostenol and selective non-prostanoid agonists like selexipag, aim to alleviate pulmonary resistance and improve exercise capacity in patients [DrugBank DB09050]. Therapeutic challenges associated with PTGIR agonists include systemic side effects such as hypotension, headache, and jaw pain due to the widespread distribution of the receptor [PubMed PMID: 26699167].

Other names

IP receptorProstanoid IP receptorPGI2 receptorPRIPRProstacyclin receptor 1

Agonist binding to the prostacyclin receptor activates Gs proteins, stimulating adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels, which leads to potent vasodilation and inhibition of platelet aggregation [UniProt P43119, DrugBank DB09050].