Role of protein kinase c in non-sensitized and passively sensitized human
isolated bronchial smooth muscle.
Rossetti, Max, Jean-Pierre Savineau, Huguette Crevel, Roger Marthan.
Laboratoire de Physiologie, Universit[acute]e de Bordeaux II, 146 rue
L[acute]eo Saignat,
33076 Bordeaux Cedex
APStracts 2:0006L, 1995.
To examine the role of protein kinase C (PKC) activation in the control of the
mechanical activity of human isolated bronchial smooth muscle obtained at
thoracotomy, the effect of the phorbol ester, phorbol 12,13 dibutyrate (PDB)
was evaluated. PDB produced slowly developing and maintained contractions
which were reduced (i) by the PKC inhibitor, staurosporine; (ii) following
long term (12h) exposure to PDB which down-regulates PKC. Moreover, the
inactive phorbol ester 4[alpha],12,13 didecanoate, had no contractile effect.
Removal of external calcium ions or addition the calcium channel antagonist
verapamil reduced the PDB-induced contraction. Passive sensitization of human
isolated bronchial rings i.e. incubation overnight of tissues in serum from
atopic asthmatic patients decreased the maximal response to PDB to 28.9 +/- 8%
of the maximal response to acetylcholine (ACh) when compared with that of
paired non-sensitized rings i.e. tissues incubated overnight in serum from
normal subjects (46.7 +/- 9.4% of the maximal response to ACh, n = 5, P <
0.05). The decrease in the response to PDB induced by either long-term pre
-exposure to PDB or passive sensitization was reversed when both types of
tissues were allowed to recover for 3h unstimulated before PDB application.
These results show that (i) PKC activation induces maintained contractions in
human isolated airway smooth muscle that are largely dependent on
extracellular calcium; (ii) passive sensitization alters the PKC-mediated
response in a way similar to that induced by prolonged stimulation of PKC.
Received 8 August 1994; accepted in final form 17 January 1995.
APS Manuscript Number L225-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.