Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons
Autor: | Ting-Ting Liu, Qi Cai, Zu-Wei Qu, Yu-Min Liu, Chun-Yu Qiu, Wang-Ping Hu, Fang Qiu |
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Rok vydání: | 2014 |
Předmět: |
Male
Nociception Agonist medicine.drug_class Narcotic Antagonists Receptors Opioid mu TRPV1 Action Potentials Pain TRPV Cation Channels (+)-Naloxone In Vitro Techniques Pharmacology Rats Sprague-Dawley chemistry.chemical_compound Dorsal root ganglion Opioid receptor Ganglia Spinal medicine Animals Molecular Biology Acid-sensing ion channel Acetic Acid Neurons Dose-Response Relationship Drug Morphine Naloxone Chemistry General Neuroscience Enkephalin Ala(2)-MePhe(4)-Gly(5) Rats Acid Sensing Ion Channels Analgesics Opioid DAMGO medicine.anatomical_structure Opioid Acid Sensing Ion Channel Blockers Neurology (clinical) Capsaicin Protons Neuroscience Developmental Biology medicine.drug |
Zdroj: | Brain Research. 1554:12-20 |
ISSN: | 0006-8993 |
Popis: | Extracellular acidosis is a common feature in pain-generating pathological conditions. Acid-sensing ion channels (ASICs), pH sensors, are distributed in peripheral sensory neurons and participate in nociception. Morphine exerts potent analgesic effects through the activation of opioid receptors for various pain conditions. A cross-talk between ASICs and opioid receptors in peripheral sensory neurons has not been shown so far. Here, we have found that morphine inhibits the activity of native ASICs in rat dorsal root ganglion (DRG) neurons. Morphine dose-dependently inhibited proton-gated currents mediated by ASICs in the presence of the TRPV1 inhibitor capsazepine. Morphine shifted the proton concentration-response curve downwards, with a decrease of 51.4±3.8% in the maximum current response but with no significant change in the pH0.5 value. Another μ-opioid receptor agonist DAMGO induced a similar decrease in ASIC currents compared with morphine. The morphine inhibition of ASIC currents was blocked by naloxone, a specific opioid receptor antagonist. Pretreatment of forskolin, an adenylyl cyclase activator, or the addition of cAMP reversed the inhibitory effect of morphine. Moreover, morphine altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. Finally, peripheral applied morphine relieved pain evoked by intraplantar of acetic acid in rats. Our results indicate that morphine can inhibit the activity of ASICs via μ-opioid receptor and cAMP dependent signal pathway. These observations demonstrate a cross-talk between ASICs and opioid receptors in peripheral sensory neurons, which was a novel analgesic mechanism of morphine. |
Databáze: | OpenAIRE |
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