The effect of signal pathway inhibitors on 5-HT release and Tph1 and VMAT1 transcription in nonflexed and rhythmically flexed KRJ-I cells. In nonflexed cells, 5-HT secretion was regulated by MAPK (A), whereas both Tph1 and VMAT1 transcription were regulated through the PKA and PI3K (PKB) pathways (C). In flexed cells, 5-HT secretion is regulated predominantly through the PKA pathway (B), whereas Tph1 and VMAT1 transcription are regulated through PKA, PI3K, and MAPK signaling (D). Values are means ± SE; n = 4. *Significant difference vs. untreated cells (P < 0.01). #Significant difference vs. nonflexed cells (P < 0.05).