The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

Vetter, Irina, Wyse, Bruce D., Monteith, Gregory R., Roberts-Thomson, Sarah J. and Cabot, Peter J. (2006) The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Molecular Pain, 2 22: 1-16. doi:10.1186/1744-8069-2-22


Author Vetter, Irina
Wyse, Bruce D.
Monteith, Gregory R.
Roberts-Thomson, Sarah J.
Cabot, Peter J.
Title The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway
Journal name Molecular Pain   Check publisher's open access policy
ISSN 1744-8069
Publication date 2006-07-16
Sub-type Article (original research)
DOI 10.1186/1744-8069-2-22
Open Access Status DOI
Volume 2
Issue 22
Start page 1
End page 16
Total pages 16
Editor Jianguo Gu
Place of publication UK
Publisher BioMed Central
Collection year 2006
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730199 Clinical health not specific to particular organs, diseases and conditions
Formatted abstract
Background: The vanilloid receptor 1 (TRPV1) is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA) pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described.

Results: In the present studies we investigated the hypothesis that the mu opioid receptor (MOP) agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+) responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-2myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1.

Conclusion: The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.
Keyword Neurosciences
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Pharmacy Publications
 
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Created: Wed, 15 Aug 2007, 10:42:05 EST