Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid receptors
| Autor: | Lieju Liu, Sidney A. Simon, Zhu-Shan Zhang, Weiguo Zhu, Gerry S. Oxford, Augustus O. Grant, Tainming Yang |
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| Rok vydání: | 2003 |
| Předmět: |
Drug
Nicotine Patch-Clamp Techniques Physiology media_common.quotation_subject Receptors Drug Nicotinic Antagonists Pharmacology Mecamylamine Kidney Sodium Channels Membrane Potentials Rats Sprague-Dawley Cricetinae medicine Animals Humans Drug Interactions Nicotinic Agonists Receptor Cells Cultured media_common Neurons Dose-Response Relationship Drug Chemistry General Neuroscience Sodium channel Alkaloid Electric Conductivity Neural Inhibition Embryo Mammalian Rats Dose–response relationship medicine.anatomical_structure nervous system Trigeminal Ganglion Capsaicin Ion Channel Gating Drug metabolism medicine.drug |
| Zdroj: | Journal of neurophysiology. 91(4) |
| ISSN: | 0022-3077 |
| Popis: | Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (approximately 41 degrees C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation. |
| Databáze: | OpenAIRE |
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