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Related Concept Videos

Drug-Receptor Interactions01:29

Drug-Receptor Interactions

Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue.
Principles of Drug Action01:24

Principles of Drug Action

Drugs are chemical substances that modify biological responses by interacting with macromolecular targets such as receptors, ion channels, transporters, and enzymes. Pharmacodynamics describes the course of action of drugs leading to the physiological effect at a specific site in the body.
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Dose-Response Relationship: Selectivity and Specificity01:25

Dose-Response Relationship: Selectivity and Specificity

Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and β2-adrenergic receptors...
Drug-Receptor Interaction: Antagonist01:28

Drug-Receptor Interaction: Antagonist

An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
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...

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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

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Retinoids selective for retinoid X receptor response pathways.

J M Lehmann1, L Jong, A Fanjul

  • 1Cancer Center, La Jolla Cancer Research Foundation, La Jolla, CA 92037.

Science (New York, N.Y.)
|December 18, 1992
PubMed
Summary

New retinoids selectively activate retinoid X receptors (RXRs) homodimers, independent of retinoic acid receptors (RARs). This allows for independent activation of distinct retinoid signaling pathways.

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Area of Science:

  • Molecular Biology
  • Endocrinology
  • Pharmacology

Background:

  • Retinoids are crucial therapeutic agents with diverse biological activities.
  • Retinoid signaling is primarily mediated by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).
  • RARs typically function as heterodimers with RXRs for DNA binding and transcriptional regulation.

Purpose of the Study:

  • To develop novel retinoids capable of selectively targeting specific retinoid receptor complexes.
  • To investigate the potential for independent activation of RXR homodimers versus RAR-RXR heterodimers.
  • To explore new therapeutic strategies by dissecting retinoid signaling pathways.

Main Methods:

  • Synthesis and characterization of a novel series of retinoids.
  • In vitro assays to assess the activation of RXR homodimers and RAR-RXR heterodimers.
  • Analysis of receptor-ligand interactions and downstream signaling effects.

Main Results:

  • A novel series of retinoids was identified that selectively activates RXR homodimers.
  • These retinoids demonstrated no significant activation of RAR-RXR heterodimers.
  • Independent modulation of RXR homodimer activity was achieved without affecting RAR-RXR heterodimer function.

Conclusions:

  • The findings demonstrate the feasibility of independently activating distinct retinoid signaling pathways.
  • This selective activation offers a new approach for fine-tuning retinoid-based therapies.
  • Targeting RXR homodimers specifically opens avenues for novel therapeutic interventions with reduced off-target effects.