2012年9月
The Mu Opioid Receptor Modulates Neurotransmission in the Rat Spinal Ventral Horn
ANESTHESIA AND ANALGESIA
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回数 : 187
- ,
- ,
- ,
- 巻
- 115
- 号
- 3
- 開始ページ
- 703
- 終了ページ
- 712
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1213/ANE.0b013e318259393d
- 出版者・発行元
- LIPPINCOTT WILLIAMS & WILKINS
BACKGROUND: Opioids inhibit excitatory neurotransmission and produce antinociception through mu opioid receptors (MORs). Although MORs are expressed in the spinal ventral horn, their functions and effects are largely unknown. Therefore, we examined the neuromodulatory effects of mu opioids in spinal lamina IX neurons at the cellular level.
METHODS: The effects of the selective mu agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]Jenkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique.
RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 mu M. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba2+ or a selective mu antagonist. Moreover, the currents were suppressed by the addition of Cs+ and tetraethylammonium or guanosine 5'-[beta-thi]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin.
CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K+ channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of mu opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity. (Anesth Analg 2012;115:703-12)
METHODS: The effects of the selective mu agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]Jenkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique.
RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 mu M. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba2+ or a selective mu antagonist. Moreover, the currents were suppressed by the addition of Cs+ and tetraethylammonium or guanosine 5'-[beta-thi]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin.
CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K+ channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of mu opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity. (Anesth Analg 2012;115:703-12)
- リンク情報
- ID情報
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- DOI : 10.1213/ANE.0b013e318259393d
- ISSN : 0003-2999
- PubMed ID : 22584545
- Web of Science ID : WOS:000307942900029