Serotonin-induced Na+/K+ pump stimulation in vascular smooth muscle cells. Evidence for coupling to multiple receptor

S S Navran1, G Allain, H F Garcia

  • 1Department of Medicine, Baylor College of Medicine, Houston, Texas.

Insights

Serotonin (5-HT) stimulates the Na+/K+ pump in canine femoral artery cells via 5-HT1 and 5-HT2 receptors, involving Na+ influx and calcium. This pump activation may oppose serotonin-induced contraction.

Area of Science:

  • Vascular smooth muscle physiology
  • Cellular signaling pathways
  • Pharmacology

Background:

  • Serotonin (5-HT) is a known contractile agonist in vascular smooth muscle.
  • The role of 5-HT in regulating ion transport, specifically the Na+/K+ pump, is less understood.
  • Investigating 5-HT's effects on ion transport provides insights into vascular tone regulation.

Purpose of the Study:

  • To investigate the effect of serotonin (5-HT) on the Na+/K+ pump activity in cultured canine femoral artery vascular smooth muscle cells.
  • To elucidate the receptor subtypes (5-HT1, 5-HT2) and signaling pathways involved in 5-HT-mediated Na+/K+ pump stimulation.
  • To determine the role of Na+ influx and intracellular calcium in 5-HT's action on the Na+/K+ pump.

Main Methods:

  • Cell culture of canine femoral artery vascular smooth muscle cells.
  • Measurement of ouabain-sensitive 86Rb uptake to assess Na+/K+ pump activity.
  • Pharmacological blockade of 5-HT receptors using ketanserin and methiothepin.
  • Assessment of Na+ influx and its modulation by dimethylamiloride.
  • Use of intracellular calcium chelator BAPTA/AM.

Main Results:

  • Serotonin (5-HT) significantly stimulated ouabain-sensitive 86Rb uptake (3.6-fold), indicating Na+/K+ pump activation.
  • Both 5-HT1 and 5-HT2 receptors mediate the 5-HT-induced pump stimulation, with 5-HT1 receptors primarily responsible for the associated Na+ influx.
  • 5-HT activated a Na+ influx pathway, likely Na+/H+ exchange, and increased intracellular calcium, both contributing to pump stimulation.
  • The 5-HT-stimulated Na+/K+ pump activation was partly inhibited by intracellular calcium chelation.

Conclusions:

  • Serotonin (5-HT) stimulates the electrogenic Na+/K+ pump in vascular smooth muscle cells.
  • This stimulation involves activation of both 5-HT1 and 5-HT2 receptors, Na+ influx via Na+/H+ exchange, and a rise in intracellular calcium.
  • The stimulation of the Na+/K+ pump by 5-HT may act as a counter-regulatory mechanism to its contractile effects.

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