Related Experiment Video

Updated: Aug 2, 2026

Assessment of Social Interaction Behaviors
06:41

Assessment of Social Interaction Behaviors

Published on: February 25, 2011

PDZ-dependent activation of nitric-oxide synthases by the serotonin 2B receptor

P Manivet1, S Mouillet-Richard, J Callebert

  • 1Centre de Recherche Claude Bernard "Pathologie Expérimentale et Communication Cellulaires," IFR 6, Service de Biochimie, Hôpital Lariboisière AP-HP, 75010 Paris, France.

The Journal of Biological Chemistry
|March 29, 2000
PubMed

Insights

5-HT(2B) receptors activate nitric oxide (NO) signaling pathways, leading to cGMP production. This involves both constitutive and inducible nitric-oxide synthase (NOS) enzymes, with PDZ interactions playing a crucial role in receptor coupling.

Area of Science:

  • Cellular biology
  • Molecular pharmacology
  • Signal transduction

Background:

  • 5-HT(2B) receptors are G protein-coupled receptors involved in various physiological processes.
  • Nitric oxide (NO) is a key signaling molecule with diverse cellular functions.
  • The precise downstream signaling pathways of 5-HT(2B) receptors are not fully elucidated.

Purpose of the Study:

  • To investigate the coupling of 5-HT(2B) receptors with nitric oxide (NO) signaling pathways.
  • To identify the molecular mechanisms underlying this receptor-NO interaction.
  • To explore the role of the PDZ motif in 5-HT(2B) receptor signaling.

Main Methods:

  • Utilized three cellular systems: 1C11 serotonergic cells, Mastomys natalensis carcinoid cells, and transfected LMTK(-) fibroblasts.
  • Stimulated 5-HT(2B) receptors and measured intracellular cGMP production.
  • Investigated the involvement of constitutive nitric-oxide synthase (cNOS) and inducible NOS (iNOS).
  • Examined the role of the PDZ motif using receptor truncation and point mutations.
  • Assessed the influence of Galpha(13) neutralization on iNOS activity.

Main Results:

  • 5-HT(2B) receptor stimulation triggers cGMP production via dual activation of cNOS and iNOS.
  • The C-terminal PDZ motif of the 5-HT(2B) receptor is essential for recruiting cNOS and iNOS.
  • Disruption of the PDZ motif or C-terminus abolished NO coupling.
  • A direct functional link between 5-HT(2B) receptor binding and cNOS activity was observed.
  • Galpha(13) is involved in the 5-HT(2B)/iNOS coupling but not cNOS activity.

Conclusions:

  • 5-HT(2B) receptors are functionally coupled to NO signaling pathways.
  • PDZ interactions are critical for mediating downstream signal transduction of the 5-HT(2B) receptor.
  • These findings reveal a novel mechanism for G protein-coupled receptor signaling and highlight potential physiological links between 5-HT(2B) receptors and NO.

More Related Videos

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells08:32

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

Published on: March 16, 2017

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model08:15

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Published on: June 6, 2025

Related Concept Videos

G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Drugs Affecting Neurotransmitter Release or Uptake01:21

Drugs Affecting Neurotransmitter Release or Uptake

Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
Antihypertensive Drugs: Vasodilators01:23

Antihypertensive Drugs: Vasodilators

Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
Antidepressant Drugs: MAOIs and Other Agents01:23

Antidepressant Drugs: MAOIs and Other Agents

Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists01:23

Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...