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Here, the ligand binding, activation, and tissue distribution of the orphan G protein-coupled receptor (GPCR) GPR92 were studied. GPR92 binds and is activated by compounds based on the lysophosphatidic acid (LPA) backbone. The binding of LPA to GPR92 was of high affinity (K D ϭ 6.4 Ϯ 0.9 nM) and led to an increase in both phosphoinositide hydrolysis and cAMP production. GPR92 is atypical in that it has a low sequence homology with the classic LPA 1-3 receptors (21-22%). Expression of GPR92 is mainly found in heart, placenta, spleen, brain, lung, and gut. Notably, GPR92 is highly expressed in the lymphocyte compartment of the gastrointestinal tract. It is the most abundant GPCR activated by LPA found in the small intestinal intraepithelial CD8 ϩ cytotoxic T cells.

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P reeclampsia remains a major problem worldwide for mothers and babies. It is estimated that yearly 50 000 women die in developing countries from preeclampsia.1 Careful maternal observation for the signs of preeclampsia and delivery of women with increasingly severe preeclampsia is the cornerstone of management (as it has been for the past 100 years). Maternal mortality is, therefore, much less in developed countries with the capacity for careful perinatal observation, but morbidity is considerable and remains the leading cause of admissions to intensive care for pregnant women.2 Also, the appropriate delivery of women who develop increasingly severe preeclampsia early in gestation accounts for 8% of all preterm births. Why No Advances in Clinical Management?During the past 20 years, there has been an explosion in our knowledge of preeclampsia. The recognition of inflammation, including endothelial dysfunction as potential unifying pathophysiological concepts and the appreciation of the multisystemic nature of preeclampsia, has directed attention away from blood pressure as the sole or even most important pathophysiological issue of preeclampsia. 4 This concept has resulted in recognition of other origins of organ dysfunction. Despite this, we have not managed to affect the management or early recognition of preeclampsia with this information. Large, well-designed multicenter, clinical intervention trials have, at best, demonstrated a minimal effect on outcome except in perhaps the highest risk cases. Attempts to use factors implicated in the pathophysiology of the disorder to predict preeclampsia have also not as yet provided adequate sensitivity and specificity to be adopted for use in routine clinical practice. 5Is There >1 Subtype of Preeclampsia?Why is this? A recurring theme is success in small studies of prediction, prevention, or treatment of preeclampsia, and failure in larger adequately powered multicenter trials. This Abstract-Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively.To that end, we present what we ...