British journal of pharmacology, 2007-08, Vol.151 (7), p.1041-1048
2007
Details
- Autor(en) / Beteiligte
- Titel
- Virodhamine and CP55,940 modulate cAMP production and IL‐8 release in human bronchial epithelial cells
- Ist Teil von
- British journal of pharmacology, 2007-08, Vol.151 (7), p.1041-1048
- Ort / Verlag
- Oxford, UK: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2007
- Link zum Volltext
- Quelle
- Wiley Online Library Database Model
- Beschreibungen/Notizen
- Background and purpose: We investigated expression of cannabinoid receptors and the effects of the endogenous cannabinoid virodhamine and the synthetic agonist CP55,940 on cAMP accumulation and interleukin‐8 (IL‐8) release in human bronchial epithelial cells. Experimental approach: Human bronchial epithelial (16HBE14o−) cells were used. Total mRNA was isolated and cannabinoid receptor mRNAs were detected by RT‐PCR. Expression of CB1 and CB2 receptor proteins was detected with Western blotting using receptor‐specific antibodies. cAMP accumulation was measured by competitive radioligand binding assay. IL‐8 release was measured by ELISA. Key results: CB1 and CB2 receptor mRNAs and proteins were found. Both agonists concentration‐dependently decreased forskolin‐induced cAMP accumulation. This effect was inhibited by the CB2 receptor antagonist SR144528, and was sensitive to Pertussis toxin (PTX), suggesting the involvement of CB2 receptors and Gi/o‐proteins. Cell pretreatment with PTX unmasked a stimulatory component, which was blocked by the CB1 receptor antagonist SR141716A. CB2 receptor‐mediated inhibition of cAMP production by virodhamine and CP55,940 was paralleled by inhibition of tumor necrosis factor‐α (TNF‐α) induced IL‐8 release. This inhibition was insensitive to SR141716A. In the absence of agonist, SR144528 by itself reduced TNF‐α induced IL‐8 release. Conclusions and implications: Our results show for the first time that 16HBE14o− cells respond to virodhamine and CP55,940. CB1 and CB2 receptor subtypes mediated activation and inhibition of adenylyl cyclase, respectively. Stimulation of the dominant CB2 receptor signalling pathway diminished cAMP accumulation and TNF‐α‐induced IL‐8 release. These observations may imply that cannabinoids exert anti‐inflammatory properties in airways by modulating cytokine release. British Journal of Pharmacology (2007) 151, 1041–1048; doi:10.1038/sj.bjp.0707320
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-1188eISSN: 1476-5381DOI: 10.1038/sj.bjp.0707320Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2042924
- Format
- –
- Schlagworte
- Adenylyl Cyclase Inhibitors, Adenylyl Cyclases - metabolism, Analgesics - pharmacology, Arachidonic Acids - pharmacology, Biological and medical sciences, Blotting, Western, Bornanes - pharmacology, Bronchi - cytology, Bronchi - drug effects, Bronchi - metabolism, cAMP, cannabinoids, Cannabinoids - pharmacology, Cell Line, Colforsin - pharmacology, CP55,940, Cyclic AMP - metabolism, Cyclohexanols - pharmacology, Dose-Response Relationship, Drug, Drug Antagonism, Epithelial Cells - cytology, Epithelial Cells - drug effects, Epithelial Cells - metabolism, human bronchial epithelium, Humans, Immunosuppressive Agents - pharmacology, Interleukin-8 - secretion, interleukin‐8, Medical sciences, Pertussis Toxin - pharmacology, Pharmacology. Drug treatments, Piperidines - pharmacology, Pyrazoles - pharmacology, Receptor, Cannabinoid, CB1 - genetics, Receptor, Cannabinoid, CB1 - metabolism, Receptor, Cannabinoid, CB2 - genetics, Receptor, Cannabinoid, CB2 - metabolism, Research Papers, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - genetics, RNA, Messenger - metabolism, Tumor Necrosis Factor-alpha - pharmacology, tumour necrosis factor‐α, virodhamine