Effects of Anandamide and Noxious Heat on Intracellular Calcium Concentration in Nociceptive DRG Neurons of Rats

As an endogenous agonist at the cannabinoid receptor CB1 and the capsaicin-receptor TRPV1, anandamide may exert both anti- and pronociceptive actions. Therefore we studied the effects of anandamide and other activators of both receptors on changes in free cytosolic calcium ([Ca2+]i) in acutely dissociated small dorsal root ganglion neurons (diameter: ≤30 μm). Anandamide (10 μM) increased [Ca2+]i in 76% of the neurons. The EC50 was 7.41 μM, the Hill slope was 2.15 ± 0.43 (mean ± SE). This increase was blocked by the competitive TRPV1-antagonist capsazepine (10 μM) and in Ca2+-free extracellular solution. Neither exclusion of voltage-gated sodium channels nor additional blockade of voltage-gated calcium channels of the L-, N-, and/or T-type, significantly reduced the anandamide-induced [Ca2+]i increase or capsaicin-induced [Ca2+]i transients (0.2 μM). The CB1-agonist HU210 (10 μM) inhibited the anandamide-induced rise in [Ca2+]i. Conversely, the CB1-antagonist AM251 (3 μM) induced a leftward shift of the co...