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CAPSAICIN- AND ANANDAMIDE-SENSITIVITY OF PRIMARY SENSORY NEURONS IS CONTROLLED BY VARIOUS COMPONENTS OF CROSSTALK BETWEEN THE CANNABINOID TYPE 1 AND THE CAPSAICIN RECEPTORS

Urban, Laszlo and Nagy, Istvan and Varga, Angelika and Selvarajah, Srikumaran and Jenes, Agnes and Kulik, Akos and Brain, Susan and Baker, David and Valente, Joao and White, John and Mackie, Kenneth and Chen, Jie (2016) CAPSAICIN- AND ANANDAMIDE-SENSITIVITY OF PRIMARY SENSORY NEURONS IS CONTROLLED BY VARIOUS COMPONENTS OF CROSSTALK BETWEEN THE CANNABINOID TYPE 1 AND THE CAPSAICIN RECEPTORS. Scientific reports, 6 (33307). pp. 1-18. ISSN 2045-2322

Abstract

The endogenous agent anandamide activates both the G protein-coupled cannabinoid type 1 (CB1) receptor and the capsaicin-responsive transient receptor potential
vanilloid type 1 ion channel (TRPV1), which exhibit a high degree of co-expression and crosstalk in primary sensory neurons (PSN). We capitalized on the dual agonist
feature of anandamide to characterize the CB1-TRPV1 crosstalk, which could be a considerable component of nociceptive processing in PSN. Although the excitatory
effect of both anandamide and capsaicin is TRPV1-dependent, a significant number of capsaicin-responsive neurons do not respond to anandamide. The CB1 receptor
antagonist rimonabant has little effect on anandamide-evoked responses or on the proportion of the anandamide- and capsaicin-responsive (ACR) neurons. However,
rimonabant reduces the amplitude of capsaicin-evoked responses in ACR, but not in capsaicin-only-responsive (COR) cells. Deletion of the CB1 receptor reduces the proportion of ACR neurons without having any effect on the overall proportion of the capsaicin-responsive neurons (ACR + COR) or on the amplitude of capsaicin- or
anandamide-evoked responses. All ACR and the great majority of COR neurons express the CB1 receptor mRNA. However, immunofluorescent staining as well as sodium dodecyl sulfate-digested freeze-fracture replica electronmicroscopy show that, the overwhelming majority of the two receptors are either in close association or
segregated in the cytoplasmic membrane of various CB1 receptor – TRPV1 coexpressing neurons. These findings suggest that the CB1-TRPV1 crosstalk has various components which, depending on the downstream effectors and spatial relationship of the two receptors, regulate the activity of the capsaicin receptor in PSN.

Item Type: Article
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/11145

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