Fig. 3.

Effect of LOX metabolites on DOR-, KOR-, and 5-HT₁-mediated inhibition of PGE₂-stimulated cAMP accumulation in primary cultures of peripheral sensory neurons (A and B) or in CHO cells transfected with either DOR or KOR(C). (A) Pretreatment with the 12-/15-LOX-dependent AA metabolites, 12-HETE (100 nM), and 15-HETE (100 nM), alone or in combination, for 15 minutes, prevented inhibition of cAMP accumulation by the KOR agonist, U50488 (100 nM), but not the 5-HT₁ receptor agonist, 5-CT (100 nM) in BK-pretreated cells. Data represent mean ± S.E.M. of five separate experiments. *P < 0.05. (B) In contrast to the effects of 12- and 15-HETE, pretreatment for 15 minutes with the 5-LOX–dependent AA metabolite 5-HETE (100 nM) had no effect on either DPDPE (DOR) or U50488 (KOR)-mediated inhibition of cAMP accumulation. (C) Pretreatment of transfected CHO cells for 15 minutes with 12-HETE (100 nM) or 15-HETE (100 nM) prevented inhibition of cAMP accumulation by the DOR agonist DPDPE or the KOR agonist U50488 (100 nM), but not the 5-HT₁ receptor agonist, 5-CT (100 nM). Data represent mean ± S.E.M. of four separate experiments. *P < 0.05 versus vehicle pretreatment condition in the absence of opioid agonist.