Related Experiment Video
Updated: Aug 8, 2026
09:32
Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)
Published on: May 7, 2013
Cannabinoid-mediated elevation of intracellular calcium: a structure-activity relationship
Gautham K Rao1, Norbert E Kaminski
1Department of Pharmacology and Toxicology, Center for Integrative Toxicology, 315 Food Safety Building, Michigan State University, East Lansing, MI 48824-1317, USA.
The Journal of Pharmacology and Experimental Therapeutics
|January 27, 2006
Summary
Tricyclic cannabinoids like Delta(9)-THC, cannabinol (CBN), and HU-210 increase intracellular calcium in T cells. This calcium influx occurs via receptor-operated cation channels, independent of CB1 and CB2 receptors, but is sensitive to antagonists.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabinol (CBN) elevate intracellular calcium ([Ca(2+)](i)) in T cells.
- CP55,940, a high-affinity CB1/CB2 ligand, does not affect [Ca(2+)](i) in T cells.
Purpose of the Study:
- To investigate the ability of various cannabinoid compounds to elevate [Ca(2+)](i) in T cells.
- To determine the dependence of this elevation on structural similarity to Delta(9)-THC and on cannabinoid receptors.
Main Methods:
- Assessed [Ca(2+)](i) changes in T cells treated with various cannabinoids.
- Utilized extracellular calcium removal, SK&F96365 (a cation channel inhibitor), and CB1/CB2 receptor antagonists.
- Employed splenocytes from wild-type and CB1(-/-)/CB2(-/-) mice.
Main Results:
- Cannabinol (CBN) and HU-210, structurally similar to Delta(9)-THC, elevated [Ca(2+)](i) in T cells.
- This elevation was dependent on extracellular calcium and inhibited by SK&F96365.
- The [Ca(2+)](i) increase was independent of CB1 and CB2 receptors but sensitive to CB1 and CB2 antagonists.
Conclusions:
- Classic tricyclic cannabinoids structurally similar to Delta(9)-THC induce robust calcium influx in T cells.
- The mechanism involves receptor-operated cation channels, not direct CB1/CB2 receptor activation.
- Cannabinoid receptor antagonists can modulate this calcium influx despite its receptor-independent nature.
Related Concept Videos
01:24Intracellular Signaling Cascades
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
01:15Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...