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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Stimulation of the Na+-K+ Pump in Cultured Guinea Pig Airway Smooth Muscle Cells by Serotonin

Kerry J. Rhoden, Alicia M. Dodson and Betty Ky
Journal of Pharmacology and Experimental Therapeutics April 2000, 293 (1) 107-112;
Kerry J. Rhoden
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Alicia M. Dodson
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Betty Ky
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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

  • Send reprint requests to: Kerry J. Rhoden, John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06519. E-mail:krhoden{at}jbpierce.org

  • ↵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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Journal of Pharmacology and Experimental Therapeutics: 293 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 1
1 Apr 2000
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Stimulation of the Na+-K+ Pump in Cultured Guinea Pig Airway Smooth Muscle Cells by Serotonin

Kerry J. Rhoden, Alicia M. Dodson and Betty Ky
Journal of Pharmacology and Experimental Therapeutics April 1, 2000, 293 (1) 107-112;

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Stimulation of the Na+-K+ Pump in Cultured Guinea Pig Airway Smooth Muscle Cells by Serotonin

Kerry J. Rhoden, Alicia M. Dodson and Betty Ky
Journal of Pharmacology and Experimental Therapeutics April 1, 2000, 293 (1) 107-112;
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