We have previously shown that amiloride, an inhibitor of several cell membrane sodium exchangers and channels including Na/H exchange and Na/Ca exchange, inhibits receptor-operated contraction of bovine airway smooth muscle. However, the precise mechanism of action of amiloride is unknown. To evalua
Effects of altered availability of Na+ on guinea-pig airway smooth muscle contractility
β Scribed by D. Raeburn
- Publisher
- Elsevier
- Year
- 1990
- Tongue
- English
- Weight
- 590 KB
- Volume
- 3
- Category
- Article
- ISSN
- 0952-0600
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β¦ Synopsis
The effects of altering the availability of sodium ions (Na+) on contractility of the guinea-pig isolated trachealis was examined using regimens which are reported to inhibit Na+/K+ ATPase activity (ouabain), Na+/H+ exchange (amiloride, ammonium ion (NH4+)) or Na+/Ca2+ exchange (reduced extracellular Na+). Inhibition of Na+/K+ ATPase and reversal of Na+/Ca2+ exchange resulted in increased 45Ca uptake and contraction of the trachealis by voltage-sensitive and voltage-insensitive mechanisms respectively. When Na+/H+ exchange was inhibited by amiloride the tissues relaxed to below their baseline tension. The relaxation was not due to reduced Ca2+ influx. Treatment with NH4+ produced a contractile response. Reduced extracellular Na+ caused a transient contraction as a result of reversal of the normal Na+/Ca2+ exchange process leading to accumulation of Ca2+ within the cell. Since the effects of amiloride and reduced extracellular sodium were different, it is unlikely that amiloride is acting primarily by inhibiting Na+/Ca2+ exchange. Amiloride reduced tissue sensitivity to methacholine and KCl without affecting Ca2+ influx. This may involve a secondary stimulation of Na+/Ca2+ exchange following changes in [Na+]i. Ouabain also reduced tissue sensitivity to methacholine and KCl. These findings suggest that Na+ are important in determining smooth muscle contractility. If NH4+ is altering pH then, at the concentrations used, the changes in [H+] were not sufficient to alter responses to the spasmogens.
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