Abstract
The cannabinoid type 1 (CB1) receptor and the capsaicin receptor (TRPV1) exhibit co-expression and complex, but largely unknown, functional interactions in a sub-population of primary sensory neurons (PSN). We report that PSN co-expressing CB1 receptor and TRPV1 form two distinct sub-populations based on their pharmacological properties, which could be due to the distribution pattern of the two receptors. Pharmacologically, neurons respond either only to capsaicin (COR neurons) or to both capsaicin and the endogenous TRPV1 and CB1 receptor ligand anandamide (ACR neurons). Blocking or deleting the CB1 receptor only reduces both anandamide- and capsaicin-evoked responses in ACR neurons. Deleting the CB1 receptor also reduces the proportion of ACR neurons without any effect on the overall number of capsaicin-responding cells. Regarding the distribution pattern of the two receptors, neurons express CB1 and TRPV1 receptors either isolated in low densities or in close proximity with medium/high densities. We suggest that spatial distribution of the CB1 receptor and TRPV1 contributes to the complexity of their functional interaction.
Highlights
Nociceptive primary sensory neurons (PSN) constitute the prototypical cell type, which expresses TRPV11,5
We cannot categorically exclude the possibility that compensatory changes in TRPV1−/− mice contribute to the lack of anandamide responsiveness, we suggest that both the anandamide- and capsaicin-evoked excitation depend on TRPV1 in PSN
All TRPV1-expressing membranes we examined exhibited immunolabelling for the cannabinoid type 1 (CB1) receptor, which was moderate to strong in general
Summary
Nociceptive primary sensory neurons (PSN) constitute the prototypical cell type, which expresses TRPV11,5. The CB1 receptor and TRPV1 exhibit co-expression in various neurons including a major sub-population of PSN in dorsal root ganglia (DRG11–13 but see[14,15]). In order to better understand how the CB1 – TRPV1 crosstalk shapes neuronal excitability, we investigated the functional interaction between the receptors, with particular attention to their spatial distribution in PSN and the effect of anandamide
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