The Effect of Sodium Transport and Calcium Channel Inhibitors on Phorbol Ester-induced Contraction of Bovine Airway Smooth Muscle
✍ Scribed by A.J. Knox; D.R. Baldwin; E.J. Cragoe Jr; P. Ajao
- Publisher
- Elsevier
- Year
- 1993
- Tongue
- English
- Weight
- 334 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0952-0600
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✦ Synopsis
SUMMARY: We studied the role of sodium transport and calcium channels in protein kinase (C) mediated signaltransduction pathways in bovine airway smooth muscle. 4- (\beta) phorbol 12,13 dibutyrate (PDB), an activator of protein kinase (C), caused dose-related slowly developing contraction in bovine bronchial rings with a peak effect at 60 (90 \mathrm{~min} .4-\alpha) PDB, an inactive analogue, was without effect. Mean peak PDB-induced contraction (measured as a percentage of the maximum response to methacholine) was reduced from (122 %) to (20 %) when experiments were carried out in calcium-free fluids + EDTA (\left(10^{-3} \mathrm{M}\right)). Similar reductions were seen in the presence of nifedipine and verapamil, inhibitors of voltage-dependent calcium channels. Amiloride at high concentrations (\left(10^{-3} \mathrm{M}\right)) reduced the contractile response to PDB from (87 %) to (20 %), but at a concentration which inhibits the sodium entry channel (\left(10^{-6} \mathrm{M}\right)), amiloride was without effect. (5-\mathrm{N}, \mathrm{N})-hexamethylene amiloride (\left(10^{-5} \mathrm{M}\right)), a specific inhibitor of (\mathrm{Na}^{+} / \mathrm{H}^{+})exchange, did not alter the contraction produced by PDB. Frusemide (\left(10^{-5} \mathrm{M}\right)), an inhibitor of (\mathrm{Na}^{+}-\mathrm{K}^{+}-\mathrm{Cl}^{-})cotransport, was without effect on PDB contractions. We conclude that phorbol ester-induced contraction of bovine airway smooth muscle is dependent on calcium entry via voltage-dependent calcium channels but is independent of (\mathrm{Na}^{+})entry, (\mathrm{Na}^{+} / \mathrm{H}^{+})exchange or (\mathrm{Na}^{+}-\mathrm{K}^{+}-\mathrm{Cl}^{-})cotransport.