Prostanoid Receptors in the Human Vascular Wall

Abstract

The mechanisms involved in vascular homeostasis and disease are mostly dependent on the interactions between blood, vascular smooth muscle, and endothelial cells. There is an accumulation of evidence for the involvement of prostanoids, the arachidonic acid metabolites derived from the cyclooxygenase enzymatic pathway, in physiological and/or pathophysiological conditions. In humans, the prostanoids activate different receptors. The classical prostanoid receptors (DP, EP1–4, FP, IP, and TP) are localized at the cell plasma or nuclear membrane. In addition, CRTH2 and the nuclear PPAR receptors are two other targets for prostanoids, namely, prostacyclin (PGI2) or the natural derivatives of prostaglandin D2. While there is little information on the role of CRTH2, there are many reports on PPAR activation and the consecutive expression of genes involved in the human vascular system. The role of the classical prostanoid receptors stimulated by PGI2 and thromboxane in the control of the vascular tone has been largely documented, whereas the other receptor subtypes have been overlooked. There is now increasing evidence that suggests a role of PGE2 and the EP receptor subtypes in the control of the human vascular tone and remodeling of the vascular wall. These receptors are also present on leukocytes and platelets, and they are implicated in most of the inflammatory processes within the vascular wall. Consequently, the EP receptor subtypes or isoforms would provide a novel and specific cardiovascular therapeutic approach in the near future.

Prostaglandin E receptor 4 (PTGER4) involved in host protection against immune challenge in oyster, Crassostrea hongkongensis

“…Earlier evidence suggested that PTGER4 mRNA is ubiquitously expressed in a variety of tissues and in most immune cell types [10,11]. In our study, it was shown that ChPTGER4 was ubiquitously expressed in all tested C. hongkongensis tissues including the gill, mantle, heart, adductor muscle, digestive gland, gonad and hemocytes, which is consistent with previous reports in mammals.…”

“…The biological actions of PGE2 are mediated by four distinct prostanoid E receptors (EP), termed PTGER1-4 (also known as EP1-4), all of which have seven transmembrane-spanning domains [7,8] and are coupled to a variety of intracellular signal transduction pathways including those that induce increases in cAMP (PTGER2 and PTGER4), decreases in cAMP (PTGER3) and of Ca 2þ mobilization (PTGER1) [8,9]. Among the PTGERs, PTGER4 is the most abundantly expressed EP subtype in a variety of immune cell types, and its functional responses have been reported in B-and T-lymphocytes, eosinophils, monocytes and macrophages [10,11]. It was reported that the PTGER4 has several sites, including S103, T168, Y186, F191, L195, S285, and D311, which were identified as being essential of the interaction of PGE2 [12].…”

Roles of Prostaglandin E2 in Cardiovascular Diseases

“…[15][16][17] Mizuguchi, et al revealed that myoelectrical activity was suppressed by continuous infusion of ONO-DI-004 into the gastric artery. This demonstrates that EP1 signaling has a crucial role in the suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying.…”

Interaction of eosinophils with endothelial cells is modulated by prostaglandin EP4 receptors

“…The EP3 receptor is coupled to the Gi protein and its activation increases the intracellular levels of Ca 21 . The EP3 receptor itself has several splice variants exhibiting some constitutive activity [16,17]. At the cellular level and in murine allergic inflammation, PGE 2 was found to inhibit eosinophil trafficking via EP2 receptor activation [18].…”