Activation of tracheal smooth muscle contraction: synergism between Ca2+ and activators of protein kinase C.

AUTOR(ES)

Park, S

RESUMO

The effects of divalent ionophores (A23187 and ionomycin), Ca2+ channel agonist (BAY K 8644), and protein kinase C (C-kinase) activators [phorbol 12-myristate 13-acetate (PMA), mezerein] on bovine tracheal smooth muscle contraction were investigated. A23187 (5 microM) and ionomycin (0.5 microM) produced a prompt but transient contraction. C-kinase activators either produced no effect--e.g., PMA at 200 nM--or produced a rise in tension that was slow in onset but then gradually increased--e.g., mezerein at 400 nM. In contrast, ionophores and C-kinase activators, in combination, acted synergistically to produce a prompt and sustained contractile response that is reminiscent of that observed in response to carbachol, a cholinergic agonist. In addition, BAY K 8644 (20 nM), which has a minimal effect on tension by itself, could significantly enhance contraction induced by C-kinase activators. The contraction induced by all of these agents was quickly reversed either by removal of extracellular Ca2+ or upon addition of forskolin, an activator of adenylate cyclase. A similar reversal of carbachol-induced contraction by forskolin was observed with carbachol-induced contraction. These findings strongly suggest that C-kinase plays an important role in mediating tracheal smooth muscle contraction.

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