Antihypertensive effect of an isolated phospholipid

LPA receptor signaling: pharmacology, physiology, and pathophysiology

“…However, there is a growing range of recognized chemical forms of LPA in various biological systems (31,32) that have been observed in concentrations spanning low nanomolar to micromolar levels. LPA concentrations in blood can range from 0.1 M in plasma and up to 10 M in serum, which is well over the apparent nanomolar K d of LPA [1][2][3][4][5][6] (23,(33)(34)(35) (36)(37)(38). Aside from blood, LPA has been quantifi ed in a variety of species, tissues, and fl uids, including neural tissue, cerebrospinal fl uid (CSF), seminal fl uid, urine, saliva, and aqueous humor (7,36,(39)(40)(41)(42)(43)(44)(45) (Table 1).…”

“…1). These receptors have signifi cantly different encoding sequences than LPA [1][2][3] , yet still bind and mediate LPA signaling effects. All six current LPA receptors are class A rhodopsin-like GPCRs with 7-transmembrane (7-TM) domains.…”

“…The diverse and numerous physiological effects of LPA are mediated through six currently recognized LPA receptors, LPA [1][2][3][4][5][6] : protein names LPA 1 -LPA 6 and gene names LPAR1-LPAR6 (human) and Lpar1-Lpar6 (nonhuman) (11,83). These 7-TM GPCRs couple to at least one or more of the four G ␣ proteins (G 12/13 , G q/11 , G i/o , and G s ) that initiate a variety of signaling cascades.…”

“…In addition, LPA affects immature and mature DCs differently. LPA [1][2][3] are expressed in both immature and mature DCs, and LPA appears to affect immature DCs by enhancing maturation and cytokine production (152,153). Furthermore, LPA 3 -specifi c activation induces chemotaxis of immature, but not mature, DCs (158).…”

“…LPAR3/Lpar3 (human chromosomal locus 1p22.3; mouse chromosome locus 3, 71.03 cM) encodes a 353 amino acid sequence GPCR with a molecular mass of ‫04ف‬ kDa that, in humans, is ‫%45ف‬ identical to LPA 1 and ‫%94ف‬ identical to LPA 2 (14). Mutagenesis studies on LPA 3 have identifi ed two specifi c residues involved in LPA 3 activation (W4.64A and R5.38N), as well as a residue that increased the EC 50 of brain, limb buds, craniofacial regions, and Rathke's pouch (89,(137)(138)(139).…”