Sinusoidal length oscillation- and receptor-mediated mRNA expression of myosin isoforms and alpha-SM actin in airway smooth muscle.

Abstract

We tested the hypothesis that sinusoidal length oscillation and receptor activation interactively regulate the abundance of mRNA encoding alpha-smooth muscle (alpha-SM) actin and myosin isoforms in intact bovine tracheal smooth muscle. We found that sinusoidal length oscillation significantly downregulated abundance of mRNA encoding alpha-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 alpha-SM actin in intact airway smooth muscle. This pattern of antagonistic interaction was also observed in cholinergic receptor activation experiments. Whereas carbachol significantly upregulated myosin heavy chain SMA isoform 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 upregulated GAPDH expression in bovine tracheal smooth muscle. However, unlike SMA expression, upregulation 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 and SMB, myosin light chain LC17a and LC17b, and alpha-SM actin in bovine tracheal smooth muscle. U0126 (10 muM) completely inhibited carbachol-induced ERK1/2 MAPK phosphorylation but did not significantly affect carbachol-induced upregulation of GAPDH and SMA expression, suggesting that the ERK1/2 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.