DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

of the TP (α and β), FP (A and B), and EP 3
(I-VI, e, f) receptors can
arise through differential mRNA splicing (Narumiya et al., 1999;
Smyth et al., 2009).
Cell Signaling Pathways and Expression. The prostanoid receptors
appear to derive from an ancestral EP receptor and share high
homology. Phylogenetic comparison of this family reveals three
subclusters: The first consists of the relaxant receptors EP 2
, EP 4
, IP,
and DP 1
, which increase cellular cyclic AMP generation; the second
consists of the contractile receptors EP 1
, FP, and TP, which
increase cytosolic levels of Ca 2+ ; and a third, consisting only of EP 3
,
Table 33–1
Eicosanoid Receptors
PRIMARY SECONDARY PRIMARY
RECEPTOR LIGAND LIGAND COUPLING MAJOR PHENOTYPE IN KNOCKOUT MICE
DP 1
PGD 2
a cAMP (G s
) b Allergic asthma
DP 2
/CHRT 2
PGD 2
15d-PGJ 2
b cAMP, a Ca 2+ (G )
i i
a or b Allergic airway inflammation
EP 1
PGE 2
PGI 2
a Ca 2+ (G )
i q
b Response of colon to carcinogens
EP 2
PGE 2
a cAMP (G s
) Impaired ovulation and fertilization
Salt-sensitive hypertension
EP 3
I-VI, e, f PGE 2
b cAMP, a Ca 2+ (G ); Resistance to pyrogens
i i
a cAMP (G s
); b Acute cutaneous inflammation
a PLC, a Ca 2+ (G ) i q
EP 4
PGE 2
a cAMP (G s
) Patent ductus arteriosus
b Bone mass/density in aged mice
a Bowel inflammatory response
b Colon carcinogenesis
FP A,B
PGF 2α
IsoPs a PLC, a Ca 2+ (G )
i q
Failure of parturition
IP PGI 2
PGE 2
a cAMP (G s
) a Thrombotic response
b Response to vascular injury
a Atherosclerosis
a Cardiac fibrosis
Salt-sensitive hypertension
b Joint inflammation
TP α,β
TxA 2
IsoPs a PLC, a Ca 2+ a Bleeding time
i
(G q
, G i
, G 12/13
, G 16
); b Response to vascular injury
a Rho, a ERK
b Atherosclerosis
activation (G q
, a Survival after cardiac allograft
G 12/13
, G 16
)
BLT 1
LTB 4
a Ca 2+ , b cAMP Some suppression of inflammatory
i
(G 16
,G i
) response
BLT 2
LTB 4
12(S)-HETE a Ca 2+ (G -like, ?
i q
12(R)-HETE G i
-like, G z
-like)
CysLT 1
LTD 4
LTC 4
/LTE 4
a PLC, a Ca 2+ (G ) b Innate and adaptive immune vascular
i q
permeability response
a Pulmonary inflammatory and fibrotic
response
CysLT 2
LTC 4
/LTD 4
LTE 4
a PLC, a Ca 2+ (G ) b Pulmonary inflammatory and
i q
fibrotic response
This table lists the major classes of eicosanoid receptors and their signaling characteristics. Splice variants for EP 3
, TP, and FP are indicated. Major
phenotypes in knockout mouse models are listed. Ca 2+ i , cytosolic Ca2+ ; cAMP, cyclic AMP; PLC, phospholipase C (activation leads to increased cellular
inositol phosphate and diacylglycerol generation and increased Ca 2+ i ); IsoPs, isoprostanes; 15d-PGJ 2 , 15-deoxy-Δ12,14 -PGJ 2
; DP 2
is a member of
the fMLP-receptor superfamily; fMLP, formyl-methionyl-leucyl-phenylalanine. See the text for other abbreviations.