Signaling mechanisms of down-regulation of voltage-activated Ca2+ channels by transient receptor potential vanilloid type 1 stimulation with olvanil in primary sensory neurons
| Autor: | Zi Zhen Wu, Shao Rui Chen, Hui Lin Pan |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Patch-Clamp Techniques Calmodulin TRPV1 TRPV Cation Channels Neurotransmission Membrane Potentials Rats Sprague-Dawley Transient receptor potential channel chemistry.chemical_compound Calcium Channels N-Type Dorsal root ganglion Ganglia Spinal medicine Animals Drug Interactions Neurons Afferent Enzyme Inhibitors Egtazic Acid Chelating Agents biology Voltage-dependent calcium channel Aryldialkylphosphatase General Neuroscience Dose-Response Relationship Radiation Neural Inhibition Immunohistochemistry Electric Stimulation Sensory neuron Rats medicine.anatomical_structure Biochemistry chemistry Capsaicin biology.protein Biophysics Calcium Channels Diterpenes Signal Transduction |
| Zdroj: | Neuroscience. 141:407-419 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2006.03.023 |
| Popis: | Olvanil ((N-vanillyl)-9-oleamide), a non-pungent transient receptor potential vanilloid type 1 agonist, desensitizes nociceptors and alleviates pain. But its molecular targets and signaling mechanisms are little known. Calcium influx through voltage-activated Ca(2+) channels plays an important role in neurotransmitter release and synaptic transmission. Here we determined the effect of olvanil on voltage-activated Ca(2+) channel currents and the signaling pathways in primary sensory neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated rat dorsal root ganglion neurons. Olvanil (1 microM) elicited a delayed but sustained inward current, and caused a profound inhibition (approximately 60%) of N-, P/Q-, L-, and R-type voltage-activated Ca(2+) channel current. Pretreatment with a specific transient receptor potential vanilloid type 1 antagonist or intracellular application of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid abolished the inhibitory effect of olvanil on voltage-activated Ca(2+) channel current. Calmodulin antagonists (ophiobolin-A and calmodulin inhibitory peptide) largely blocked the effect of olvanil and capsaicin on voltage-activated Ca(2+) channel current. Furthermore, calcineurin (protein phosphatase 2B) inhibitors (deltamethrin and FK-506) eliminated the effect of olvanil on voltage-activated Ca(2+) channel current. Notably, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin antagonists, and calcineurin inhibitors each alone significantly increased the amplitude of voltage-activated Ca(2+) channel current. In addition, double immunofluorescence labeling revealed that olvanil induced a rapid internalization of Ca(V)2.2 immunoreactivity from the membrane surface of dorsal root ganglion neurons. Collectively, this study suggests that stimulation of non-pungent transient receptor potential vanilloid type 1 inhibits voltage-activated Ca(2+) channels through a biochemical pathway involving intracellular Ca(2+)-calmodulin and calcineurin in nociceptive neurons. This new information is important for our understanding of the signaling mechanisms of desensitization of nociceptors by transient receptor potential vanilloid type 1 analogues and the feedback regulation of intracellular Ca(2+) and voltage-activated Ca(2+) channels in nociceptive sensory neurons. |
| Databáze: | OpenAIRE |
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