We tested the hypothesis that sinusoidal length oscillation and receptor activation interactively regulate the abundance of mRNA encoding -SM actin and myosin isoforms in intact bovine tracheal smooth muscle. We found that sinusoidal length oscillation significantly down-regulated abundance of mRNA encoding -SM actin mRNA in unstimulated tissues, but not in histamine- and carbachol-activated tissues. This observation suggests antagonistic interactions between mechanical stretch and receptor-mediated signal transduction in regulating the abundance of mRNA encoding -SM actin in intact airway smooth muscle. This pattern of antagonistic interaction was also observed in cholinergic receptor activation experiments. Whereas carbachol significantly up-regulated SMA myosin heavy chain expression in muscle strips held at slack length, carbachol did not significantly alter SMA expression in muscle strips at sinusoidal length oscillation. Carbachol also significantly up-regulated GAPDH expression in bovine tracheal smooth muscle. However, unlike SMA expression, up-regulation of GAPDH expression mediated by cholinergic receptor activation appeared to be insensitive to the mechanical state of airway smooth muscle. Unlike carbachol, histamine did not significantly alter the expression of GAPDH, myosin heavy chain SMA, SMB, myosin light chain LC17a, LC17b, and -SM actin in bovine tracheal smooth muscle. U0126 (10 µM) completely inhibited carbachol-induced Erk 1/2 MAPK phosphorylation, but did not significantly affect carbachol-induced up-regulation of GAPDH and SMA expression, suggesting that Erk 1/2 MAPK pathway was not the underlying mechanism. A potential implication of these findings is that periodic stretching of airways during respiratory cycles may modulate mRNA expression by receptor agonists in airway smooth muscle cells, in vivo.