Prostaglandin receptors: their role in regulating renal function

Renal cyclooxygenase-1 and cyclooxygenase-2 actively metabolize arachidonat e to metabolism five primary prostanoids: prostaglandin E-2, prostaglandin F-2a, prostaglandin I-2, thromboxane A(2), and prostaglandin D-2. These lip id mediators interact with a family of distinct G-protein-coupled prostanoi d receptors designated EP, FP, IF, TP, and DP, respectively, which exert im portant regulatory effects on renal function. The intrarenal distribution o f these prostanoid receptors has been mapped and the consequences their act ivation are being characterized. The FP, TP, and EP1 receptors preferential ly couple to increased cell Ca2+. EP2, EP4, DP, and IP receptors stimulate cyclic adenosine monophosphate, whereas the EP3 receptor preferentially cou ples to Gi, inhibiting cyclic adenosine monophosphate generation. EP1 and E P3 messenger RNA expression predominate in the collecting duct and thick li mb, respectively, where their stimulation reduces sodium chloride and water absorption, promoting natriuresis and diuresis. Interestingly, only a mild change in renal water handling is seen in the EP3 receptor knockout mouse. Although only low levels EP2 receptor messenger RNA are detected in kidney and its precise intrarenal localization is uncertain, mice with targeted d isruption of the EP2 receptor display salt-sensitive hypertension, suggesti ng it also plays an important role in salt excretion. In contrast, EP4 mess enger RNA is readily detected in the glomerulus where it may contribute to the regulation of renin release and decrease glomerular resistance. TP rece ptors are also highly expressed in the glomerulus, where they may increase glomerular vascular resistance. The IP receptor messenger RNA is most highl y expressed in the afferent arteriole and it may also modulate renal arteri al resistance and renin release. At present there is little evidence for DP receptor expression in the kidney. Together these receptors act as physiol ogic buffers that protect the kidney from excessive functional changes duri ng periods of physiologic stress. Loss of the combined effects of these rec eptors contributes to the side effects seen in the setting of nonsteroidal anti-inflammatory drug administration, whereas selective antagonists for th ese receptors may provide new therapeutic approaches in disease. Curr Opin Nephrol Hypertens 9:23-29. (C) 2000 Lippincott Williams & Wilkins.