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The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway.
Mol Pain. 2006 Jul 16; 2:22.MP

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-12-myristate-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.

Authors+Show Affiliations

The School of Pharmacy, The University of Queensland, Brisbane, 4072, Australia. i.vetter@pharmacy.uq.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16842630

Citation

Vetter, Irina, et al. "The Mu Opioid Agonist Morphine Modulates Potentiation of Capsaicin-evoked TRPV1 Responses Through a Cyclic AMP-dependent Protein Kinase a Pathway." Molecular Pain, vol. 2, 2006, p. 22.
Vetter I, Wyse BD, Monteith GR, et al. The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Mol Pain. 2006;2:22.
Vetter, I., Wyse, B. D., Monteith, G. R., Roberts-Thomson, S. J., & Cabot, P. J. (2006). The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Molecular Pain, 2, 22.
Vetter I, et al. The Mu Opioid Agonist Morphine Modulates Potentiation of Capsaicin-evoked TRPV1 Responses Through a Cyclic AMP-dependent Protein Kinase a Pathway. Mol Pain. 2006 Jul 16;2:22. PubMed PMID: 16842630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. AU - Vetter,Irina, AU - Wyse,Bruce D, AU - Monteith,Gregory R, AU - Roberts-Thomson,Sarah J, AU - Cabot,Peter J, Y1 - 2006/07/16/ PY - 2006/04/03/received PY - 2006/07/16/accepted PY - 2006/7/18/pubmed PY - 2006/9/28/medline PY - 2006/7/18/entrez SP - 22 EP - 22 JF - Molecular pain JO - Mol Pain VL - 2 N2 - 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-12-myristate-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. SN - 1744-8069 UR - https://www.unboundmedicine.com/medline/citation/16842630/The_mu_opioid_agonist_morphine_modulates_potentiation_of_capsaicin_evoked_TRPV1_responses_through_a_cyclic_AMP_dependent_protein_kinase_A_pathway_ L2 - https://journals.sagepub.com/doi/10.1186/1744-8069-2-22?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -