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.
Yang
K X
KX
Department of Pharmacology, University of Sydney, NSW, Australia.
Black
J L
JL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D019311:Staurosporine
D000470:Alkaloids; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D010879:Piperazines; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; C070515:bisindolylmaleimide I