FIGURE 2.

Peptidomimetic PAR₂ agonists stimulate an increase in impedance in model epithelial cells. 16HBE14o- cells were plated onto coated E-plates and monitored as described under “Experimental Procedures.” Each agonist, 2-f-LIGRLO-NH₂, 2-at-LIGRL-NH₂, or 6-an-LIGRL-NH₂, was applied to the cells in a dose-response assay, and the cell index was measured every 15 s for 4 h. A, C, and E, acute responses to each agonist over 30 min. B, D, and F, prolonged responses to each agonist over 4 h. Both 2-f-LIGRLO-NH₂ and 2-at-LIGRL-NH₂ display a slightly faster response with a higher potency than that observed with 6-an-LIGRL-NH₂. Each agonist was evaluated for efficacy and potency from four independent experiments using either the peak response or the area under the curve. G, EC₅₀ values of each agonist calculated from the peak response: 2-f-LIGRLO-NH₂, 235 nm; 2-at-LIGRL-NH₂, 314 nm; and 6-an-LIGRL-NH₂, 403 nm. H, EC₅₀ values of each agonist calculated from the area under the curve: 2-f-LIGRLO-NH₂, 114 nm; 2-at-LIGRL-NH₂, 106 nm; and 6-an-LIGRL-NH₂, 254 nm. Error bars in G and H represent mean ± S.E.