Prostaglandin receptors orprostanoid receptors represent a sub-class of cell surface membranereceptors that are regarded as the primary receptors for one or more of the classical, naturally occurringprostanoids viz.,prostaglandin D2, (i.e.PGD2),PGE2,PGF2alpha,prostacyclin (PGI2),thromboxane A2 (TXA2), andPGH2.[1] They are named based on the prostanoid to which they preferentially bind and respond, e.g. the receptor responsive to PGI2 at lower concentrations than any other prostanoid is named the Prostacyclin receptor (IP). One exception to this rule is the receptor for thromboxane A2 (TP) which binds and responds to PGH2 and TXA2 equally well.
All of the prostanoid receptors areG protein-coupled receptors belonging to theSubfamily A14 of the rhodopsin-like receptor family except for the Prostaglandin DP2 receptor which is more closely related in amino acid sequence and functionality to chemotactic factor receptors such as the receptors forC5a andleukotriene B4.[2]
Prostanoid receptors bind and respond principally to metabolites of the straight chainpolyunsaturated fatty acid (PUFA),arachidonic acid. These metabolites contain twodouble bonds and are named series 2 prostanoids, i.e. PGD2, PGE2, PGF2α, PGI2, TXA2 and PGH2. However, the same enzymes that metabolize arachidonic acid to series 2 prostanoids similarly metabolize two other straight chain PUFAs: they metabolizegamma-Linolenic acid, which has one less double bond than arachidonic acid, to series 1 prostanoids (PGD1, PGE1, etc.), which have one less double bond than the series 2 prostanoids, and they metabolizeeicosapentaenoic acid, which has one more double bond than arachidonic acid, to series 3 prostanoids (PGD3, PGE3, etc.), which have one more double bond than the series 2 prostanoids. In general, receptors for the series 2 prostanoids also bind with and respond to the series 1 and 3 prostanoids. Typically, prostanoid receptors show somewhat less affinity and responsiveness to the 1 and 3 series prostanoids.[3]
There are 9 established prostanoid receptors. The following table gives these receptors:a) full name;b) shortened names;c) activating prostanoids (presented in order of decreasing potencies);[4]d) time-honored classification as contractile (i.e. contracting smooth muscle), relaxant (i.e. relaxing smooth muscle), or inhibitory (i.e. inhibiting adenyl cyclase (AC) production ofcyclic AMP [cAMP]);[5]e) G proteins types to which they link and activate, i.e. those containing theGs alpha subunit,Gi alpha subunit,Gq alpha subunit and/orG12 subunit;[2][4] andf) signaling pathways which they regulate includingAdenyl cyclase which when activated increases cellularcAMP and when inhibited reduces the cellular levels of thissecondary messenger;Phosphoinositide 3-kinase which when activated is responsible for formingphosphatidylinositol 3-phosphate,phosphatidylinositol (3,4)-bisphosphate, andphosphatidylinositol (3,4,5)-trisphosphate secondary messengers;Phospholipase C (PLC) which when activated is responsible for formingInositol trisphosphate (IP3) anddiacylglycerol secondary messengers that are, respectively, responsible for raising the levels of Ca2+ in the cellular cytosol to control the activity of Ca2+-cell signaling agents and for activatingprotein kinase C (PKC) secondary messengers; andExtracellular signal-regulated kinases (ERK),p38 mitogen-activated protein kinases (p38 Mpk), andcAMP response element-binding protein (CREB) which when activated phosphorylate and thereby influence the activity of key proteins that govern cell function.[2]
| Full name | shortened name | activating prostanoids | classification[5] | G protein linkage[2] | pathways[2] |
|---|---|---|---|---|---|
| Prostaglandin DP1 receptor | DP1 | PGD2>>PGE2>PGF2α>PGI2=TXA2[6] | relaxant | Gs alpha subunit | activates AC, increases cAMP, raises Ca2+ |
| Prostaglandin DP2 receptor | DP2 | PGD2>>PGF2α=PGE2>PGI2=TXA2[7] | ? | Gi alpha subunit | inhibits AC to depress cAMP levels |
| Prostaglandin EP1 receptor | EP1 | PGE2>PGF2α=PGI2>PGD2=TXA2[8] | contractile | Gq alpha subunit | stimulates PLC, IP3, PKC, ERK, p38 Mpk, and CREB |
| Prostaglandin EP2 receptor | EP2 | PGE2>PGF2α=PGI2>PGD2=TXA2[9] | relaxant | Gs alpha subunit | stimulates AC, raises cAMP, stimulatesbeta catenin and Glycogen synthase kinase 3 |
| Prostaglandin EP3 receptor | EP3 | PGE2>PGF2α,PGI2>PGD2=TXA2[10] | inhibitory | Gi &G12 subunit | inhibits AC, decreases cAMP, stimulates PLC & IP3, raises Ca2+ |
| Prostaglandin EP4 receptor | EP4 | PGE2>PGF2α=PGI2>PGD2=TXA2[11] | relaxant | Gs alpha subunit | stimulates AC, PKA, PI3K, AKT, ERK, p38 Mpk, & CREB; raises cAMP |
| Prostaglandin F2α receptor | FP | PGF2α>PGD2>PGE2>PGI2=TXA2[12] | contractile | Gq alpha subunit | stimulates PLC, IP3, & PKC; raises Ca2+ |
| Prostacyclin I2 receptor | IP | PGI2>>PGD2=PGE2=PGF2α>TXA2[13] | relaxant | Gs alpha subunit | stimulates AC & PKA; raises cAMP |
| Thromboxane A2 receptor | TP | TXA=PGH2>>PGD2=PGE2=PGF2α=PGI2[14] | contractile | Gq alpha subunit | stimulates PLC & IP3; raises Ca2+ |
There is indirect evidence for a second PGI2 receptor inBEAS-2B human airway epithelial cells but this finding has not been collaborated and the putative receptor has not been otherwise defined.[15]