The involvement of protein kinase C in the contraction of human airway smooth muscle.

The involvement of protein kinase C in the contraction of airway smooth muscle has been investigated in human isolated bronchus. Phorbol 12,13-dibutyrate (PDB) (10 microM) produced aw biphasic response--relaxation followed by contraction. The protein kinase C inhibitor, staurosporine (0.1 microM) reduced the contractile response to PDB from 89 +/- 2.9% to 53 +/- 4.5% of the response to 1 mM acetylcholine (P < 0.05, n = 6) but increased the relaxation response from 12 +/- 6.1% to 29 +/- 5% (P < 0.05, n = 6). Staurosporine also reduced the maximal contractile response to a single dose of histamine (10 microM) from 121 +/- 13% to 91 +/- 10% (P < 0.05, n = 4) and the sustained phase tension from 94 +/- 4% to 85 +/- 5% at 30 min (P < 0.05, n = 4). However, GF 109203X, a more selective inhibitor of protein kinase C at 0.1 microM, 1 microM and 10 microM had no effect on the maximal contractile response and reduced only the sustained phase of the contraction to histamine. These results suggest that protein kinase C plays a role in maintenance of contraction in human airway smooth muscle.