Prostacyclin Receptor

Prostacyclin receptor is a receptor for prostacyclin (a prostaglandin that is also called prostaglandin I2, PGI2). Its HGNC name is prostaglandin I2 (prostacyclin) receptor (IP) (symbol PTGIR; older synonymous symbol IP).It is a member of the G protein–coupled receptor family. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor.

1187856-49-0
Ralinepag
1187856-49-0
BMY 45778
152575-66-1
176391-41-6
ONO-1301
176391-41-6
B0084-475745
MRE-269
475085-57-5
B0084-136086
Treprostinil
81846-19-7

Background


An Overview of Prostacyclin Receptor

Prostacyclin receptor (also named the prostaglandin I2 receptor, IP) is a seven transmembrane G-protein coupled receptor of the rhodopsin-like receptor family, Subfamily A14. Prostacyclin receptor is encoded in humans by the prostacyclin receptor gene (PTGIR). PTGIR spans approximately 7000 bases along chromosome 19 (locus 19q13.3), and is comprised of 3 exons separated by two introns, one intron lying upstream from the ATG start codon and the other placing at the end of the sixth transmembrane helix. Prostacyclin receptor binds to and mediates the biological actions of prostacyclin (PGI2). Prostacyclin is released by vascular endothelial cells and serves as a potent vasodilator, inhibitor of platelet aggregation (anti-thrombotic), and moderator of vascular smooth muscle cell proliferation –migration–differentiation (anti-atherosclerotic). Prostacyclin receptors are most highly expressed in the brain and thymus and are easily detected in most other tissues. Prostacyclin receptors find endothelial cells and smooth muscle cells throughout the vascular network.

Inhibition of Prostacyclin Receptor

Selexipag is an oral selective prostacyclin receptor agonist that relaxes smooth muscle walls, dilates blood vessels, and reduces pressure on the pulmonary arteries. RO1138452, RO3244794, TG6-129 and BAY-73-1449 are some synthetic prostacyclin receptor antagonists. Their binding to the prostacyclin receptor does not activate the prostacyclin receptor.

Prostacyclin Receptorand diseases

Numerous studies using prostacyclin receptor knockout mice have shown an increased propensity for thrombosis, intimal hyperplasia and restenosis, and reperfusion injury in mice lacking the prostacyclin receptor. More recently, prostacyclin receptor activity has been shown to have atherosclerotic protection, especially in premenopausal women. Many in vivo studies suggest a dysfunctional prostacyclin receptor activity have related to many cardiovascular diseases, including stroke, myocardial infarction, and hypertension. Although many functions are defined in animal model studies, the primary clinical application of prostacyclin receptor is as a vasodilator: an irritant of prostacyclin receptor for the treatment of serious and even life-threatening diseases involving pathological vasoconstriction.

References:

Jeremiah, S., Eric, J. A., Scott, R. G., Karen, L. D., John, H. (2007) Human prostacyclin receptor structure and function from naturally-occurring and synthetic mutations. Prostaglandins & other Lipid Mediators, 82: 95–108.