TABLE 2

Correlation of LPA receptor mRNA expression and Ki16425 inhibition of Ca2+ responses to LPA and other agonists in different cell types

Effects of Ki16425 on [Ca2+]i increase induced by LPA and other receptor agonists in various cell types, including THP-1 cells, 3T3 fibroblasts, A431 cells, PC-12 cells, and HL-60 cells. These cells were incubated in the presence or absence of Ki16425 (10 μM). LPA receptor expression was assessed from Northern blotting and PCR methods shown in Fig. 8.

Cell Type and LPA Receptor Expression Ligand Ca2+ Response Ca2+ Response to Ligand + 10 μM Ki16425
THP-1 LPA (nM)
LPA1 10 432 ± 4 24 ± 5*
LPA2 ATP (nM)
LPA4 300 231 ± 26 221 ± 27
PAF (nM)
10 317 ± 32 295 ± 3
SPC (μM)
30 74 ± 8 65 ± 3
3T3 LPA (nM)
LPA1 100 906 ± 60 151 ± 20*
LPA2 PDGF (pM)
LPA4 40 419 ± 43 429 ± 7
400 793 ± 50 776 ± 2
S1P (nM)
10 451 ± 76 397 ± 49
100 913 ± 80 820 ± 103
A431 LPA (nM)
LPA1 10 711 ± 8 12 ± 5*
LPA2 EGF (nM)
LPA3 16.7 206 ± 13 180 ± 5
PAF (nM)
1 459 ± 32 385 ± 27
PC-12 LPA (nM)
LPA1 10 64 ± 6 45 ± 5*
100 362 ± 17 304 ± 13*
1000 375 ± 8 333 ± 22
HL-60 LPA (μM)
LPA2 1 39 ± 3 37 ± 1
LPA4 10 41 ± 4 47 ± 8
SPC (μM)
3 116 ± 23 111 ± 22
30 305 ± 8 298 ± 51
LPC (μM)
3 34 ± 8 34 ± 10
30 171 ± 33 157 ± 29
Psy (μM)
3 57 ± 5 63 ± 9
30 176 ± 17 163 ± 2
2AG (μM)
26 39 ± 8 31 ± 6
  • LPC, lysophosphatidylcholine; Psy, psychosine; 2AG, 2-arachidonoylglycerol.

  • * The effect of Ki16425 is significant.