Effects of okadaic acid on the human isolated bronchus

The effects of okadaic acid, a polyether derivative of a 38-carbon monocarboxylic fatty acid obtained from a culture of the marine dinoflagellate, Prorocentrum lima, were studied on the human isolated bronchus. In low concentrations (0.01 and 0.03 microM), okadaic acid had no significant effect of its own on the human isolated bronchus, but in higher concentrations (0.1-10 microM) it induced a series of contractions and relaxations. The first contraction was of low intensity (5% of maximum response to acetylcholine 3 mM) and occurred early. The second contraction had a higher amplitude (30% of maximum response to acetylcholine 3 mM) and reached its peak with okadaic acid 0.3 microM. At higher concentrations (1-10 microM), following a relaxation phase, a later rebound contraction occurred between 70 and 120 min and corresponded to 40% of the maximum response to acetylcholine 3 mM. In addition, okadaic acid inhibited or abolished the contractile response evoked by either KCl 60 mM or acetylcholine 3 mM with IC50 of 0.04 and 0.12 microM, respectively. The second contraction evoked by 0.3 microM okadaic acid was partially inhibited in the presence of the Ca2+ channel blocker, nicardipine 1 microM, or after incubation of the human bronchus in a Ca(2+)-free solution and it was completely abolished in the presence of CdSO4 0.1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)