Page 342 - Basic _ Clinical Pharmacology ( PDFDrive )

328 SECTION IV Drugs with Important Actions on Smooth Muscle

TABLE 18–1 Eicosanoid receptors. 1

Receptor Endogenous Secondary G Protein; Second
(Human) Ligand Ligands Messenger Major Phenotype(s) in Knockout Mice

DP 1 PGD 2 G s ; ↑cAMP ↓Allergic asthma
↑Inflammatory cardiovascular disease, hypertension,
thrombosis
2+
G i ; ↑Ca , ↓cAMP ↑Allergic airway inflammation
DP 2 PGD 2 15d-PGJ 2 i
↓Cutaneous inflammation
EP 1 PGE 2 PGI 2 G q ; ↑Ca 2+ i ↓Colon carcinogenesis
G s ; ↑cAMP Impaired fertilization
EP 2 PGE 2
Salt-sensitive hypertension
↓Tumorgenesis
G i ; ↓cAMP, ↑Ca 2+ Resistance to pyrogens
EP 3 I, II, III, IV, V, VI, e, f PGE 2 i
G s ; ↑cAMP ↓Acute cutaneous inflammation
G q ; ↑PLC, ↑Ca 2+ i ↑Allergic airway inflammation
G 12/13 ; Rho activation Obesity
G s ; ↑cAMP ↑Myocardial infarction severity
EP 4 PGE 2
↑Intestinal inflammatory/immune response
↓Colon carcinogenesis
Patent ductus arteriosus
FP A,B PGF 2α isoPs G q ; ↑PLC, ↑Ca 2+ i Parturition failure
G 12/13 ; Rho activation ↓Basal blood pressure; ↑Vasopressor response
↓Atherosclerosis
IP PGl 2 PGE 2 Gs; ↑cAMP ↑Thrombotic response
↑Response to vascular injury
↑Atherosclerosis
↑Cardiac fibrosis
Salt-sensitive hypertension
isoPs G q ,G 12/13 ,G 16 ; ↑PLC, ↑Bleeding time
TP α,β TXA 2
2+
↑Ca , Rho activation
i
↓Response to vascular injury
↓Atherosclerosis
↑Survival after cardiac allograft
2+
G 16 ,G i ; ↑Ca , ↓cAMP Inflammatory responses
BLT 1 LTB 4 i
↓Insulin resistance in obesity
BLT 2 LTB 4 12(S)-HETE G q -like, G i -like, G 12 -like, ↓inflammatory arthritis
2+
↑Ca i
12(R)-HETE ↑Experimental colitis
G q ; ↑PLC, ↑Ca 2+ ↓Innate and adaptive immune vascular permeability
CysLT 1 LTD 4 LTC 4 /LTE 4 i
response
↑Pulmonary inflammatory and fibrotic response
G q ; ↑PLC, ↑Ca 2+ ↓Pulmonary inflammatory and fibrotic response
CysLT 2 LTC 4 /LTD 4 LTE 4 i
1
Splice variants for the eicosanoid receptors are indicated where appropriate.
2+
Ca , intracellular calcium; cAMP, cyclic adenosine 3’,5’-monophosphate; PLC, phospholipase C; isoPs, isoprostanes; 15d-PGJ 2 , 15-deoxy-Δ 12,14 -PGJ 2 .
i