Effects of Anandamide and Noxious Heat on Intracellular Calcium Concentration in Nociceptive DRG Neurons of Rats
| Autor: | Wolfgang Greffrath, Tilo Fischbach, Rolf-Detlef Treede, Hermann Nawrath |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Hot Temperature
Cannabinoid receptor Polyunsaturated Alkamides Physiology TRPV1 TRPV Cation Channels Arachidonic Acids Pharmacology Calcium in biology Rats Sprague-Dawley chemistry.chemical_compound Ganglia Spinal Physical Stimulation Animals Drug Interactions Dronabinol Egtazic Acid Chelating Agents Neurons Calcium metabolism Analysis of Variance Dose-Response Relationship Drug Chemistry General Neuroscience Extracellular Fluid Anandamide Calcium Channel Blockers Endocannabinoid system Rats Nociception Calcium Capsaicin Endogenous agonist Endocannabinoids |
| Zdroj: | Journal of Neurophysiology. 98:929-938 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.01096.2006 |
| Popis: | 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+]iin 76% of the neurons. The EC50was 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+]iincrease or capsaicin-induced [Ca2+]itransients (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 concentration-response relationship by ∼4 μM ( P < 0.001; Hill slope, 2.17 ± 0.75). Intracellular calcium transients in response to noxious heat (47°C for 10 s) were highly correlated with the anandamide-induced [Ca2+]iincreases ( r = 0.84, P < 0.001). Heat-induced [Ca2+]itransients were facilitated by preincubation with subthreshold concentrations of anandamide (3 μM), an effect that was further enhanced by 3 μM AM251. Although anandamide acts on both TRPV1 and CB1 receptors in the same nociceptive DRG neurons, its pronociceptive effects dominate. Anandamide triggers an influx of calcium through TRPV1 but no intracellular store depletion. It facilitates the heat responsiveness of TRPV1 in a calcium-independent manner. These effects of anandamide differ from those of the classical exogenous TRPV1-agonist capsaicin and suggest a primarily modulatory mode of action of anandamide. |
| Databáze: | OpenAIRE |
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