Abstract: AimTo determine the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the expression of endothelin receptor type B (ET_B) during culture. MethodsSB386023, a specific inhibitor for ERK1/2 pathway, was used to define the intracellular signaling pathway for the up-regulation of ET_B receptors and sarafotoxin 6c (S6c), a selective agonist for ET_B receptors，induced contraction in isolated rat superior mesenteric arteries. The contraction was recorded by a sensitive in vitro myograph and the receptor mRNA was quantified by a real-time PCR. The phosphorylated ERK1/2 proteins were analyzed by phosphoELISA assay. ResultsS6c induced strong contractile responses of the artery after culture for 24 h, while there was no response to S6c in fresh vessel segments. The enhanced contractile response to S6c paralleled with an increase of mRNA for ET_B receptors. The phosphorylated ERK1/2 proteins significantly increased after culture for 3 h. After co-culture with SB386023 for 24 h, S6c-induced contractions significantly decreased with reduction of Emax from (217±14)% to (127±23)% (P<0.01). This response paralleled with a decreased level of ET_B receptor mRNA. Conclusion ERK1/2 pathway was involved in the up-regulation of ET_B receptors on smooth muscle cells isolated from rat mesenteric arteries during culture.