Table 1.

LPA receptors: expression, functions, and intracellular signaling mediators

Receptor	G protein	Action	Expression/observations	References
LPAR1 or Edg2	Gα12/13, Gαq/11 and Gαi	Cellular proliferation, serum response elements, MAPK, PLC, Akt, and Rho activation, adenylyl cyclase inhibition, Ca2+ mobilization, and YAP/Taz activation	First receptor identified for LPA. Its expression is in the uterus, brain, testis, small intestine, lung, heart, kidney, stomach, spleen, placenta, thymus, and skeletal muscle (adult human and mice). Its expression is more restricted during embryonic development, including portions of the brain, limb buds, dorsal olfactory bulb, somites, craniofacial region, and genital tubercle.	32
LPAR2 or Edg4	Gα12/13, Gαq/11 and Gαi	Cellular proliferation, serum response elements, MAPK, PLC, Akt, and Rho activation, adenylyl cyclase inhibition, and Ca2+ mobilization	Shows 55% amino acid similarity to LPAR1. During development its expression is at limb buds, brain, Rathke’s pouch, and craniofacial regions. This receptor is high expressed in testis and leukocytes (human and mouse); and kidney, testis, and uterus (mouse). More moderate levels of this receptor are found in the spleen, prostate, pancreas and thymus (human), and lower levels are found in the stomach, lung, spleen, postnatal brain, thymus, and heart (mouse).	33
LPAR3 or Egd7	Gαq/11 and Gαi	MAPK and PKC activation, Ca2+ mobilization, adenylyl cyclase inhibition, and YAP/Taz activation	During development its expression is observed in the mesonephros, heart, and in three spots in the otic vesicle (mouse). In the adult, its expression is most prominent in the testis, heart, pancreas, and prostate (human and mouse) as well as kidney, lung, testis, and uterus (mouse). It is less highly expressed in the ovary, lung and brain (human); and brain, small intestine, heart, placenta, thymus, stomach, and spleen (mouse).	12,34,35
LPAR4 or P2Y9 or GPR23	Gα12/13, Gαq/11, Gαi and Gαs	Cellular proliferation, serum response elements, MAPK, PLC, Akt, and Rho activation, adenylyl cyclase inhibition, and Ca2+ mobilization	During development, it is found in the embryonic brain, branchial arches, maxillary processes, liver, limb buds, and somites (mouse). In adults, it is prominently found in the ovary, while less prominent in the pancreas, thymus, brain, small intestine, heart, testis, colon, prostate, and spleen (human). It is present in ovary, heart, thymus, skin, and bone marrow (mouse).	36
LPAR5 or GPR92/93	Gα12/13 and Gαq/11,	Ca2+ mobilization and PLC activation	LPAR5 shares 35% homology with LPAR4. It is highly expressed in spleen, and to a lesser degree in placenta, heart, colon, small intestine, and liver (human). It is highly expressed in small intestine and more moderately in heart, lung, stomach, spleen, colon, skin, thymus, platelets, liver, gastrointestinal lymphocytes, mast cells, and dorsal root ganglia (mouse). During development, it was found in the early embryonic mouse rostral midbrain, forebrain, and hindbrain (mouse).	3–5,35,38,39
LPAR6- P2Y5	Gα12/13, Gαq/11 Gαi and Gαs	Rho activation	Little is known about this receptor, however, genetic studies indicated roles for LPA6 in hypotrichosis simplex, a complex of diseases involving familial hair loss.	3–5,35,38,39
GPR87	Gα12/13, Gαq/11 and Gαi	Intracellular Ca2+ increase	It is expressed at high levels in testis and brain and in other tissues, such as placenta, ovary, prostate, and skeletal muscle in a lower level, but it is not expressed in heart, lung, kidney, liver, or intestine	64
P2Y10	Gαq/11	Intracellular Ca2+ increase	It is expressed at high levels in appendix, lymph node; and spleen; more moderately in bone marrow, colon, duodenum, reproductive organs, brain, lung, and skeletal muscle.	69
TRPV1	Ca+2 channel		It is expressed at high levels in duodenum, ovary, skin, small intestine; more moderately in adrenal, appendix, brain, colon, endometrium, kidney, liver, placenta, prostate, spleen, stomach, gall bladder, fat, testis, thyroid, and urinary bladder.	70,71