Tropisetron upregulates cannabinoid CB(1) receptors in cerebellar granule cells: Possible involvement of calcineurin.
Summary of "Tropisetron upregulates cannabinoid CB(1) receptors in cerebellar granule cells: Possible involvement of calcineurin."
Tropisetron, a selective 5-HT(3) receptor antagonist, is widely used to counteract chemotherapy-induced emesis. Some investigations describe disparate effects including immunomodulatory properties for tropisetron which may be mediated through immunophilin-calcineurin pathway. Calcineurin, a phosphatase involved in immune system signaling, modulates expression of several genes, such as Cannabinoid type one (CB(1)) receptors. On the quest for its underlying mechanisms of action, this study aimed to investigate the effect of tropisetron on calcineurin activity and CB(1) receptor expression and function in cerebellar granule neurons (CGNs). The rat pup CGNs were used as highly calcineurin-rich and devoid of 5-HT(3) receptor neuronal cells. Calcineurin activity was assessed in CGNs treated with tropisetron or the congener granisetron at 1nM-10μM concentrations. Moreover, cannabinoid CB(1) receptor expression at mRNA and protein levels were investigated by real time PCR and western blotting, respectively and its functionality studied by measuring the secondary messenger cAMP in CGNs receiving tropisetron or granisetron. Results indicate that tropisetron, but not granisetron, significantly inhibits the phosphatase activity of calcineurin, over-expresses the CB(1) receptors at both transcriptional and protein levels, and reduces cAMP content. Our investigation shows that tropisetron targets calcineurin in a receptor-independent fashion. Tropisetron-induced CB(1) receptor up-regulation might underlie many pharmacological aspects of tropisetron unrelated to anti-emesis.
Affiliation
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Journal Details
This article was published in the following journal.
Name: Brain research
ISSN: 1872-6240
Pages: 1-8
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21914553
- DOI: http://dx.doi.org/10.1016/j.brainres.2011.08.050
Medical and Biotech [MESH] Definitions
Receptor, Cannabinoid, Cb2
A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.
Receptor, Cannabinoid, Cb1
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
Endocannabinoids
Endogenous compounds that bind to CANNABINOID RECEPTORS. They are structurally different from the CANNABINOIDS which are primarily derived from plants.
Nasal Mucosa
The mucous lining of the NASAL CAVITY, including lining of the nostril (vestibule) and the OLFACTORY MUCOSA. Nasal mucosa consists of ciliated cells, GOBLET CELLS, brush cells, small granule cells, basal cells (STEM CELLS) and glands containing both mucous and serous cells.
Receptors, Cannabinoid
A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.
PubMed Articles
Purinergic Modulation of Granule Cells.
Extracellular purines exert their action in the nervous system through purinergic neurotransmission and neuromodulatory processes. Among brain areas, efforts have been made to investigate the purinerg...
Pharmacological characterization of the cannabinoid CB(1) receptor PET ligand ortholog, (3)HMePPEP.
MePPEP ((3R,5R)-5-(3-methoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one) is an inverse agonist shown to be an effective PET ligand for labeling cannabinoid CB(1)...
Cerebellar granule cells are generated postnatally in humans.
How many cerebellar granule cells are generated pre- or postnatally in human is unknown. Using a rigorous design-based stereologic approach we investigated postmortem cerebella from 14 children who di...
Early growth response factor 1 (Egr-1) is induced during activity deprivation-dependent apoptosis in cerebellar granule neurons and plays a critical role in neuronal apoptosis. It has been proposed th...
Chemical probes for the recognition of cannabinoid receptors in native systems.
Receptors made visible: The described biotin-tagged small-molecule probes with excellent affinities for the CB(1) and CB(2) cannabinoid receptors (CB(1) R and CB(2) R) enable direct visualization of t...
Clinical Trials
Clinical Confirmation of a Pharmacodynamic Interaction Between Tropisetron and Paracetamol
A previous study has shown that tropisetron inhibits the analgesic effect of paracetamol in healthy volunteers. This study aims at confirming this pharmacodynamic interaction in patients w...
Imaging of Cannabinoid Receptors Using New Radioactive Tracer
This study will test a new radioactive tracer, [(11)C]MePPEP, for use in positron emission tomography (PET) imaging. The tracer is used to visualize cannabinoid receptors, proteins in the...
This study will determine the effectiveness of tropisetron plus risperidone in improving cognitive and perceptual disturbances and symptoms in Chinese people with schizophrenia.
Imaging Cannabinoid CB1 Receptors in Alcohol Dependence
The cannabinoid type 1 (CB1) receptor is a protein found in the brain that is involved with the effects of marijuana; it may also play a role in the effects of alcohol dependence and withd...
Imaging Cannabinoid CB1 Receptors in Schizophrenia
Background: - The CB1 receptor is a protein in the brain that is targeted by the active ingredients in cannabis (marijuana). Brain systems that react to cannabis may be involved in the ca...
