Abstract
The effect of 5-hydroxytryptamine (5-HT) or serotonin on Na+-K+ pump activity of airway smooth muscle was investigated by measuring 86Rb+ uptake in cultured guinea pig tracheal smooth muscle cells.86Rb+ uptake consisted of three distinct components, one sensitive to ouabain, one to bumetanide, and one insensitive to either inhibitor. 5-HT induced a concentration-dependent increase in ouabain-sensitive 86Rb+ uptake (EC50 = 21 nM) but had no effect on bumetanide-sensitive uptake, suggesting that it stimulates the Na+-K+ pump but not the Na+-K+-Cl− cotransporter. Ouabain-sensitive uptake also was stimulated by the 5-HT2A/2C agonists 2,5-dimethoxy-4-iodoamphetamine and α-methyl-5-HT, but not by the 5-HT1 agonist 5-carboxamidotryptamine, the 5-HT1A/1B/2C agonist 1-(3-chlorophenyl)piperazine, or the 5-HT3 agonist 1-(3-chlorophenyl)biguanide. 5-HT-stimulated86Rb+ uptake was inhibited by the 5-HT2A antagonists ketanserin and spiperone, but not by the 5-HT1A antagonist NAN 190 or the 5-HT3antagonist Y25310. 5-HT-stimulated 86Rb+ uptake was inhibited by reducing extracellular Na+ concentration and by the Na+-H+ exchange inhibitors dimethylamiloride and 5-(N-methyl-N-isobutyl)-amiloride. These observations suggest that 5-HT stimulates the Na+-K+ pump of airway smooth muscle via 5-HT2A receptors by a mechanism dependent on Na+ influx, possibly through the Na+-H+ exchanger. Because stimulation of the Na+-K+ pump produces hyperpolarization, this may represent a negative-feedback mechanism that opposes contraction in response to 5-HT.
Footnotes
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Send reprint requests to: Kerry J. Rhoden, John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06519. E-mail:krhoden{at}jbpierce.org
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↵1 This work was supported by Grant HL54114 from the National Heart Lung and Blood Institute.
- Abbreviations:
- 5-HT
- 5-hydroxytryptamine (serotonin)
- ASM
- airway smooth muscle
- BSS
- balanced salt solution
- DMA
- dimethylamiloride
- DOI
- 2,5-dimethoxy-4-iodoamphetamine
- MIA
- 5-(N-methyl-N-isobutyl)-amiloride
- 5-CT
- 5-carboxamidotryptamine
- mCPP
- 1-(3-chlorophenyl)-piperazine
- mCPB
- 1-(3-chlorophenyl)biguanide
- PLSD
- protected least significant difference
- Received September 7, 1999.
- Accepted December 10, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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