Related Experiment Video

Updated: Jul 16, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
09:39

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

Published on: January 27, 2014

The enhancement of dopamine D1 receptor desensitization by adenosine A1 receptor activation

Yan Cao1, Ke-Qiang Xie, Xing-Zu Zhu

  • 1Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. ycao@sibs.ac.cn

European Journal of Pharmacology
|March 21, 2007
PubMed

Insights

Adenosine A(1) receptors potentiate dopamine D(1) receptor desensitization. Blocking adenosine A(1) receptors or endogenous adenosine attenuated this desensitization, highlighting a regulatory role in dopamine signaling.

Area of Science:

  • Neuropharmacology
  • Cellular signaling

Background:

  • Dopamine D(1) receptors are crucial for neurotransmission.
  • Receptor desensitization impacts cellular responses.
  • Adenosine A(1) receptors modulate various cellular processes.

Purpose of the Study:

  • To investigate the role of adenosine A(1) receptors in dopamine D(1) receptor desensitization.
  • To elucidate the signaling pathways involved in this interaction.

Main Methods:

  • Utilized a human embryonic kidney 293 cell line stably co-expressing adenosine A(1) and dopamine D(1) receptors (A(1)D(1) cells).
  • Employed cAMP accumulation assays to measure receptor activity.
  • Administered agonists (SKF38393, CPA) and antagonists (DPCPX) for adenosine A(1) and dopamine D(1) receptors.
  • Used pertussis toxin and adenosine deaminase to probe signaling pathways and endogenous adenosine effects.

Main Results:

  • Long-term dopamine D(1) receptor agonist (SKF38393) exposure induced rapid dopamine D(1) receptor desensitization.
  • Coadministration of an adenosine A(1) receptor agonist (CPA) potentiated SKF38393-induced desensitization.
  • This potentiation was blocked by an adenosine A(1) receptor antagonist (DPCPX) and was G(i) protein-independent.
  • Blocking endogenous adenosine also attenuated dopamine D(1) receptor desensitization.

Conclusions:

  • Adenosine A(1) receptors play a significant role in regulating dopamine D(1) receptor desensitization.
  • Adenosine A(1) receptor activation potentiates ligand-induced dopamine D(1) receptor desensitization.
  • This interaction is mediated by adenosine A(1) receptors in a G(i) protein-independent manner.

More Related Videos

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology07:25

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology

Published on: March 27, 2018

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine06:40

Combined Infusion and Stimulation with Fast-Scan Cyclic Voltammetry (CIS-FSCV) to Assess Ventral Tegmental Area Receptor Regulation of Phasic Dopamine

Published on: April 23, 2020

Related Concept Videos

Adrenergic Agonists: Indirect-Acting Agents01:25

Adrenergic Agonists: Indirect-Acting Agents

Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
Drugs Affecting Neurotransmitter Synthesis01:29

Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
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...
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...