ArticleBritish journal of pharmacology2011
Characterization of the endocannabinoid system, CB(1) receptor signalling and desensitization in human myometrium.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Differential Expression of CBCannabis and cannabinoid research · 2022Article
- (Endo)Cannabinoids and Gynaecological Cancers.Cancers · 2020Review
- CBAdvances in pharmacology (San Diego, Calif.) · 2017Review
- Marijuana, the Endocannabinoid System and the Female Reproductive System.The Yale journal of biology and medicine · 2016Review
- Inhibitory signaling by CB1 receptors in smooth muscle mediated by GRK5/β-arrestin activation of ERK1/2 and Src kinase.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- The K2/Spice phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products.Drug metabolism reviews · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe endocannabinoid plays vital roles in several aspects of reproduction, including gametogenesis, fertilization and parturition. However, little is known regarding the presence or role of the endocannabinoid system in myometrial function. Here the presence of the endocannabinoid system and signalling properties of cannabinoid receptors were characterized. EXPERIMENTAL APPROACH: Components of the endocannabinoid system were identified using qRT-PCR, immunohistochemical, immunoblotting and radioligand binding experiments. Cannabinoid receptor signalling pathways were characterized using standard MAPK and second messenger assays. KEY
resultsPrimary myometrium expresses the endocannabinoid synthesizing enzyme N-acyl-phosphatidyl ethanolamine-specific phospholipase D, endocannabinoid degrading enzyme fatty acid amide hydrolase and cannabinoid CB(1) , but not CB(2) receptors or transient receptor potential vanilloid-type-1 channels. The CB(1) receptor ligand anandamide caused a Gα(i/o) -dependent inhibition of adenylate cyclase reducing intracellular cAMP levels, and Gα(i/o) , phosphoinositide-3-kinase, Src-kinase-dependent ERK activation. CB(1) receptor-generated signals declined following continual anandamide stimulation, possibly due to ligand metabolism since free anandamide concentrations declined during the experiment from 2.5 µM initially, to 500 nM after >30 min. However, identical loss of CB(1) receptor responsiveness occurred in the presence of the metabolically stable derivative methanandamide. Moreover, RNAi-mediated depletion of arrestin3 (a negative regulator of receptor signalling) prevented loss of CB(1) receptor activity, enhancing and prolonging ERK signals. CONCLUSIONS AND IMPLICATIONS: The myometrium has the capacity to synthesize, respond to and degrade endocannabinoids. Furthermore, reduced CB(1) receptor responsiveness occurs as a consequence of receptor desensitization, not agonist depletion and we identify a key role for arrestin3 in this process.
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