Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Intrathecal PKA-selective siRNA treatment blocks sustained morphine-mediated pain sensitization and antinociceptive tolerance in rats.

Journal of neuroscience methods·2011
Same author

Sustained morphine-mediated pain sensitization and antinociceptive tolerance are blocked by intrathecal treatment with Raf-1-selective siRNA.

British journal of pharmacology·2010
Same author

Water-protein interactions.

Biophysical journal·2009
Same author

Picosecond decay kinetics and quantum yield of fluorescence of the photoactive yellow protein from the halophilic purple phototrophic bacterium, Ectothiorhodospira halophila.

Biophysical journal·2009
Same author

Plasmon waveguide resonance spectroscopic evidence for differential binding of oxidized and reduced Rhodobacter capsulatus cytochrome c2 to the cytochrome bc1 complex mediated by the conformation of the Rieske iron-sulfur protein.

Biochemistry·2007
Same author

Binding of oxidized and reduced cytochrome c2 to photosynthetic reaction centers: plasmon-waveguide resonance spectroscopy.

Biochemistry·2004
Same journal

(R)-STU104 and Brefeldin-A Synergistically Enhance the Therapeutic Effect On IBD By Inhibiting the TAK1-MKK3-P38 Signaling Pathway.

Current molecular pharmacology·2025
Same journal

Corrigendum to: IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway.

Current molecular pharmacology·2025
Same journal

Corrigendum to: An Essential Role of c-Fos in Notch1-mediated Promotion of Proliferation of KSHV-Infected SH-SY5Y Cells.

Current molecular pharmacology·2025
Same journal

Corrigendum to: Progress of Angiogenesis Signal Pathway and Antiangiogenic Drugs in Nasopharyngeal Carcinoma.

Current molecular pharmacology·2025
Same journal

Corrigendum to: Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review.

Current molecular pharmacology·2025
Same journal

Network Pharmacology and Bioinformatics of Flavonoids from <i>Scutellaria baicalensis stems</i>: Mitigating Aβ-Induced Cognitive Impairment in Rats <i>via</i> the MEK-ERK-CREB Pathway.

Current molecular pharmacology·2025
See all related articles

Related Experiment Video

Updated: Jun 17, 2026

Synthesis of a Deuterated Standard for the Quantification of 2-Arachidonoylglycerol in Caenorhabditis elegans
14:25

Synthesis of a Deuterated Standard for the Quantification of 2-Arachidonoylglycerol in Caenorhabditis elegans

Published on: September 21, 2019

Functional selectivity in cannabinoid signaling.

E V Varga1, T Georgieva, S Tumati

  • 1University of Arizona, College of Medicine, Department of Pharmacology, Tucson, AZ 85724, USA. evarga@email.arizona.edu

Current Molecular Pharmacology
|December 22, 2009
PubMed
Summary
This summary is machine-generated.

Novel cannabinoid (CB) pharmaceuticals with fewer side effects are needed. Different CB agonists stabilize unique CB receptor conformations, leading to functional selectivity in signaling pathways, enabling targeted drug design.

More Related Videos

Tobacco Hornworm as an Insect Model System for Cannabinoid Pre-clinical Studies
05:25

Tobacco Hornworm as an Insect Model System for Cannabinoid Pre-clinical Studies

Published on: December 29, 2021

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells
09:21

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells

Published on: November 7, 2025

Related Experiment Videos

Last Updated: Jun 17, 2026

Synthesis of a Deuterated Standard for the Quantification of 2-Arachidonoylglycerol in Caenorhabditis elegans
14:25

Synthesis of a Deuterated Standard for the Quantification of 2-Arachidonoylglycerol in Caenorhabditis elegans

Published on: September 21, 2019

Tobacco Hornworm as an Insect Model System for Cannabinoid Pre-clinical Studies
05:25

Tobacco Hornworm as an Insect Model System for Cannabinoid Pre-clinical Studies

Published on: December 29, 2021

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells
09:21

BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells

Published on: November 7, 2025

Area of Science:

  • Pharmacology
  • Neuroscience
  • Biophysics

Background:

  • Cannabinoid (CB) agonists have therapeutic potential but cause side effects.
  • Understanding CB receptor signaling is crucial for developing safer drugs.
  • Novel strategies are needed to identify CB pharmaceuticals with improved side effect profiles.

Purpose of the Study:

  • To investigate whether structurally distinct CB agonists induce functional selectivity in CB receptor signaling.
  • To provide direct experimental evidence for the hypothesis that different CB agonist classes stabilize unique receptor conformations.

Main Methods:

  • Review of experimental data on CB agonist signaling.
  • In vitro and in vivo studies assessing CB agonist potency and G protein activation.
  • Plasmon-waveguide resonance (PWR) spectroscopy to directly observe CB1 receptor conformational changes.

Main Results:

  • Structurally diverse CB agonists exhibit selectivity for different intracellular signaling pathways.
  • Chemically distinct CB agonists show varying potencies for analgesia and other CNS effects.
  • PWR experiments confirmed that different CB agonists induce distinct CB1 receptor conformational changes, leading to functional selectivity in G protein activation.

Conclusions:

  • Different classes of CB agonists stabilize unique active CB receptor conformations.
  • This conformational selectivity explains functional selectivity in CB receptor signaling.
  • Targeting specific receptor conformations offers a strategy for designing improved CB analgesics with reduced side effects.