Abstract
Cannabinoid receptor agonists structurally parallel TRPV1 agonists. Both endocannabinoids and endovanilloids resemble membrane derived phospholipids. In spinal dorsal horn, TRPV1 and CB1 co‐localize. Can single compounds crossover to activate both receptors? Can activation of one receptor influence function of the other? Support for both CB1/TRPV1 interactions exists. Here we examined CB1 and TRPV1 receptor activation in synaptic transmission by solitary tract afferents (ST) in horizontal slices of the solitary tract nucleus (NTS). The CB1 selective compound ACEA (10 μM) depressed excitatory postsynaptic current amplitude (ST‐EPSCs) in 78% of ST afferents (TRPV1+, capsaicin sensitive, −38 ± 7% n=14 vs. TRPV1‐ −37 ± 10%, n= 7) but CB1‐ afferents were uncommon. In addition, CB1 activation increased synaptic failures only in TRPV1+. ACEA did not alter spontaneous EPSCs frequency or amplitude. WIN 55,212–2 (10 μM) had identical actions. ACEA actions were blocked by CB1 antagonist AM251 (10 μM). CB1 activation or block failed to alter temperature driven changes in basal or spontaneous EPSCs that depend on TRPV1. The results indicate widespread presynaptic CB1 and suggest that CB1 selectively targets action potential dependent glutamate release likely by inhibiting voltage dependent calcium channels (decreasing release probability) and action currents that depolarize terminals (synaptic failures).
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