Fig. 1.

Lysophosphatidic acid (LPA)/LPA5R signaling in polarized epithelial cells stimulates Na⁺/H⁺ exchanger 3 (NHE3) activity. LPA stimulates NHE3 activity, but this only occurs in the presence of both Na⁺/H⁺ exchanger regulatory factor 2 (NHERF2) and LPA5R (A). The LPA/LPA5R stimulation of NHE3 requires the epidermal growth factor receptor (EGFR; B), Rho/Rho-associated kinase (ROCK; C), ERK (D), and elevated intracellular Ca²⁺ (E). Results are means ± SE of initial rates of NHE3 activity in polarized opossum kidney (OK) cells with inhibitors preincubated for 30 min. LPA stimulation and effects of inhibitors were similar after 2, 30, and 60 min of LPA exposure; results shown are for 2 and 30 min (combined) of LPA exposure. Concentration and number of experiments for each condition were as follows: LPA in A (n > 4 for all conditions); the EGFR inhibitor AG1478 (25 nM; n = 6); the Rho/ROCK inhibitor Y27632 (50 μM; n = 6); the ERK inhibitor U0126 (10 μM; n = 5); and BAPTA-AM (10 μM; n = 4). CTRL, control.