Related Experiment Video
Updated: Aug 8, 2026

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography
Published on: September 22, 2011
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.
Abstract:
Exposure of cultured canine femoral artery vascular smooth muscle cells to serotonin (5-HT) caused a 3.6-fold stimulation of ouabain-sensitive 86Rb uptake. The 5-HT2 receptor antagonist, ketanserin, partly blocked the 5-HT-mediated Na+/K+ pump stimulation and the 5-HT1/5-HT2 receptor antagonist, methiothepin, completely blocked the response, suggesting that both 5-HT1 and 5-HT2 receptors play a role in the 5-HT-mediated Na+/K+ pump activation. Second messengers generated by 5-HT2 receptor-mediated phosphoinositide hydrolysis, Ins(1,4,5)P3 and diacylglycerol were implicated in the stimulatory action of 5-HT on the vascular Na+/K+ pump. Like some other contractile agonists, 5-HT activated a Na+ influx pathway which caused Na+/K+ pump stimulation by increasing the rate-limiting substrate. The maximum stimulation of Na+ influx by 5-HT was 2.5-fold. The 5-HT-stimulated Na+ influx was totally blocked by methiothepin but only 29% inhibited by ketanserin, indicating that most of the Na+ influx was mediated by the 5-HT1 receptor. The 5-HT-stimulated Na+ influx was substantially inhibited by 50 microM dimethylamiloride, suggesting that the Na+ influx pathway stimulated by 5-HT was Na+/H+ exchange. BAPTA/AM 1,2-[bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra (acetoxymethyl) ester], an intracellular Ca++ chelator, partly blocked 5-HT-stimulated Na+ influx and ouabain-sensitive 86Rb uptake, suggesting that Ca++ is an important mediator of these responses. These data suggest that: 1) 5-HT, in addition to its well known activity as a contractile agonist, can stimulate the electrogenic Na+/K+ pump which, in theory, would tend to oppose contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
More Related Videos
Related Concept Videos
G-protein Coupled Receptors
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Drugs Affecting Neurotransmitter Release or Uptake
Smooth Muscle Contraction
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

