Fig. 4.

Effect of the 12-/15-LOX-dependent AA metabolites, 12- and 15-HETE, on DOR- and KOR-mediated activation of ERK in primary cultures of peripheral sensory neurons (A and B) or in CHO cells transfected with either DOR or KOR (C). Cells were pretreated for 15 minutes with 12-HETE (1 µM) and 15-HETE (1 µM) in combination, followed by 15 minutes’ incubation with BK (10 µM). Cells were then incubated with the DOR agonist DPDPE (100 nM) (A) or the KOR agonist U50488 (100 nM) (B) for the times indicated. (C) CHO cells transiently transfected with DOR or KOR were treated with 12-HETE (1 µM) and 15-HETE (1 µM) in combination for 15 minutes before incubation with DPDPE (100 nM) or U50488 (100 nM) for the times indicated. For all experiments, the levels of pERK were determined as described in Materials and Methods. Pretreatment with 12- and 15-HETE did not alter the magnitude or the time course for increases in ERK activation in response to either DPDPE or U50488. P > 0.05, two-way analysis of variance.