Theophylline attenuates Ca sensitivity and modulates BK channels in porcine tracheal smooth muscle
British Journal of Pharmacology, ISSN: 0007-1188, Vol: 140, Issue: 5, Page: 939-947
2003
- 19Citations
- 13Captures
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Metrics Details
- Citations19
- Citation Indexes19
- 19
- CrossRef15
- Captures13
- Readers13
- 13
Article Description
1 Theophylline, a nonselective phosphodiesterase inhibitor, has long been regarded as a major bronchodilator in the treatment of human asthma. Using front-surface fluorometry with fura-2 and α-toxin permeabilization, the effects of theophylline on intracellular Ca concentration ([Ca ] ), tension development and Ca sensitivity of the contractile apparatus were investigated in porcine tracheal smooth muscle strips. 2 Application of theophylline induced a relaxation without a significant decrease in [Ca ] when strips were precontracted by 40 mM K depolarization, while theophylline significantly decreased both [Ca ] and tension induced by carbachol. 3 The effects of theophylline on the increases in [Ca ] and tension induced by carbachol were significantly inhibited by iberiotoxin, an inhibitor of large-conductance Ca -activated K channels. 4 In the absence of extracellular Ca , theophylline significantly attenuated carbachol-induced transient increases in tension development, while it did not affect carbachol-induced transient increase in [Ca ] . 5 The [Ca ] -force relationship, which was determined by cumulative applications of extracellular Ca (0-5 mM) during 40 mM K depolarization, was significantly shifted to the right by theophylline. 6 In α-toxin permeabilized strips, theophylline significantly increased the EC value of [Ca ] for contraction and enhanced the effect of cAMP, but not of cGMP. 7 These results indicate that theophylline induces relaxation of the porcine tracheal smooth muscle through an activation of BK channels, and a resultant decrease in [Ca ] and an attenuation of Ca sensitivity, presumably through the action of cAMP.
Bibliographic Details
Wiley
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