Urban, Laszlo, Nagy, Istvan, Varga, Angelika, Selvarajah, Srikumaran, Jenes, Agnes, Kulik, Akos, Brain, Susan, Baker, David, Valente, Joao, White, John, 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