Targeting PGE2 Receptor Subtypes Rather Than Cyclooxygenases: A Bridge Over Troubled Water?

Table 1.

The Pleiotropic Action of PGE2: Phenotypes of EP Knockout Mice

Genetic deletion Inflammation/Immunity Carcinogenesis Reproduction Kidney Lung Central or peripheral nervous system Bone Gastro- intestinal tract
Numbers in parentheses indicate references. MLR, mixed lymphoid reaction; AOM, azoxymethane; NMDA, N-Methyl-D-Aspartate; PTH, parathyroid hormone.
↓ indicates reduction; ↑ indicates enhancement.
EP1−/ − No effect on MLR (10) ↓ Early and AOM-induced colon cancer (24) ↓ Airway responsiveness (27) ↓ Inflammationdependent fever (26)
 ↓ NMDA- induced stroke (28) ↓ Gastric mucosal integrity (25)
EP2−/ − ↓ PGE2-dependent MLR inhibition (10) ↓ skin and colon tumors (12, 15)
 ↓ Tumor angiogenesis (13)
 ↓ Mammary gland hyperplasia (14) ↓ Ovulation and fertilization (11) ↓ Hypotensive effect of PGE2 (9)
 Saltsensitive hypertension (9)
 ↓ Renin secretion rate (9) ↓ PGE2- induced bronchodilation (9) ↓ Spinal PGE2-evoked hyperalgesia (16)
 ↑Stroke after artery occlusion or NMDA (17, 18) ↓ Osteoclastogenic response to PGE2, PTH, and 1,25- OH Vitamin D3 (9)
EP3−/ − ↑Allergic inflammation (21)
 No effect on MLR (10) ↑Colon cancer development induced by AOM (22) ↓ Capacity of urinary concentration (23) ↓ Pyrogen-dependent fever (23) No effect on gastric mucosal protection (25)
 Acid induced bicarbonate secretion from duodenum (23)
EP4−/ − ↓ Arthritis (9) ↓ PGE2-dependent MLR inhibition (10)
 ↓ Migration of APC cells (9)
 ↓ Skin hypersensitivity ↓ Aberrant colic foci by AOM (9) ↓ Renin secretion rate (9) ↑Infarct in ischemiareperfusion injury (20) ↓ Bone mass (9)
 ↓ Repair from fractures (19) ↓ Intestine mucosal barrier (25)

This Article

  1. MI April 2006 vol. 6 no. 2 68-73