Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Presynaptic modulation of synaptic transmission in rat subthalamic nucleus (STN) neurons was investigated using whole-cell patch-clamp recordings in brain slices. Evoked GABAergic inhibitory postsynaptic currents (IPSCs) were reversibly reduced by methionine enkephalin (ME) with an IC50 value of 1.1 ± 0.3 μM. The action of ME was mimicked by the μ-selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), and was partially blocked by the μ-selective antagonists naloxonazine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Evoked GABAA IPSCs were also inhibited by the δ-selective agonist [D-Pen2,5] -enkephalin (DPDPE), but not by the κ-selective agonist (+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl) -1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) and the orphan receptor agonist orphanin FQ/nociceptin (OFQ). DPDPE-induced inhibition was completely blocked by the δ-selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). ME, DAMGO and DPDPE increased the paired-pulse ratio of IPSCs. Evoked excitatory postsynaptic currents (EPSCs) were reversibly reduced by ME with an IC50 value of 0.35 ± 0.14 μM. Inhibition by ME was associated with an increase in the paired-pulse ratio of EPSCs. The action of ME was mimicked by DAMGO, and blocked by naloxonazin. DPDPE had little effect on evoked EPSCs. Neither U-69593 nor OFQ had any effect. ME significantly decreased the frequency of spontaneous miniature EPSCs (mEPSCs) without change in their amplitude. The action of ME was mimicked by DAMGO. DPDPE had no effect. The presynaptic voltage-dependent potassium conductance blocker 4-aminopyridine (4-AP, 100 μM) abolished the inhibitory effects of ME on evoked IPSCs and EPSCs. In contrast, 4-AP only partially blocked the actions of baclofen. These results suggest that opioids inhibit inhibitory synaptic transmission in the STN through the activation of presynaptic μ- and δ-receptors. In contrast, inhibition of excitatory synaptic inputs to the STN occurs through the activation of only μ-receptors. Both inhibitions may be mediated by blockade of voltage-dependent potassium conductance.

Original languageEnglish (US)
Pages (from-to)219-230
Number of pages12
JournalJournal of Physiology
Volume541
Issue number1
DOIs
StatePublished - May 15 2002

Fingerprint

Subthalamic Nucleus
Methionine Enkephalin
Opioid Receptors
Synaptic Transmission
D-Penicillamine (2,5)-Enkephalin
Enkephalins
Excitatory Postsynaptic Potentials
Inhibitory Postsynaptic Potentials
Inhibitory Concentration 50
Benzeneacetamides
Potassium
Presynaptic Receptors
In Vitro Techniques
4-Aminopyridine
Baclofen
Opioid Analgesics
Neurons

ASJC Scopus subject areas

  • Physiology

Cite this

@article{672648679ee640df88fa179506f65c51,
title = "Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro",
abstract = "Presynaptic modulation of synaptic transmission in rat subthalamic nucleus (STN) neurons was investigated using whole-cell patch-clamp recordings in brain slices. Evoked GABAergic inhibitory postsynaptic currents (IPSCs) were reversibly reduced by methionine enkephalin (ME) with an IC50 value of 1.1 ± 0.3 μM. The action of ME was mimicked by the μ-selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), and was partially blocked by the μ-selective antagonists naloxonazine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Evoked GABAA IPSCs were also inhibited by the δ-selective agonist [D-Pen2,5] -enkephalin (DPDPE), but not by the κ-selective agonist (+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl) -1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) and the orphan receptor agonist orphanin FQ/nociceptin (OFQ). DPDPE-induced inhibition was completely blocked by the δ-selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). ME, DAMGO and DPDPE increased the paired-pulse ratio of IPSCs. Evoked excitatory postsynaptic currents (EPSCs) were reversibly reduced by ME with an IC50 value of 0.35 ± 0.14 μM. Inhibition by ME was associated with an increase in the paired-pulse ratio of EPSCs. The action of ME was mimicked by DAMGO, and blocked by naloxonazin. DPDPE had little effect on evoked EPSCs. Neither U-69593 nor OFQ had any effect. ME significantly decreased the frequency of spontaneous miniature EPSCs (mEPSCs) without change in their amplitude. The action of ME was mimicked by DAMGO. DPDPE had no effect. The presynaptic voltage-dependent potassium conductance blocker 4-aminopyridine (4-AP, 100 μM) abolished the inhibitory effects of ME on evoked IPSCs and EPSCs. In contrast, 4-AP only partially blocked the actions of baclofen. These results suggest that opioids inhibit inhibitory synaptic transmission in the STN through the activation of presynaptic μ- and δ-receptors. In contrast, inhibition of excitatory synaptic inputs to the STN occurs through the activation of only μ-receptors. Both inhibitions may be mediated by blockade of voltage-dependent potassium conductance.",
author = "Ke-Zhong Shen and Steven Johnson",
year = "2002",
month = "5",
day = "15",
doi = "10.1113/jphysiol.2001.013404",
language = "English (US)",
volume = "541",
pages = "219--230",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro

AU - Shen, Ke-Zhong

AU - Johnson, Steven

PY - 2002/5/15

Y1 - 2002/5/15

N2 - Presynaptic modulation of synaptic transmission in rat subthalamic nucleus (STN) neurons was investigated using whole-cell patch-clamp recordings in brain slices. Evoked GABAergic inhibitory postsynaptic currents (IPSCs) were reversibly reduced by methionine enkephalin (ME) with an IC50 value of 1.1 ± 0.3 μM. The action of ME was mimicked by the μ-selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), and was partially blocked by the μ-selective antagonists naloxonazine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Evoked GABAA IPSCs were also inhibited by the δ-selective agonist [D-Pen2,5] -enkephalin (DPDPE), but not by the κ-selective agonist (+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl) -1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) and the orphan receptor agonist orphanin FQ/nociceptin (OFQ). DPDPE-induced inhibition was completely blocked by the δ-selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). ME, DAMGO and DPDPE increased the paired-pulse ratio of IPSCs. Evoked excitatory postsynaptic currents (EPSCs) were reversibly reduced by ME with an IC50 value of 0.35 ± 0.14 μM. Inhibition by ME was associated with an increase in the paired-pulse ratio of EPSCs. The action of ME was mimicked by DAMGO, and blocked by naloxonazin. DPDPE had little effect on evoked EPSCs. Neither U-69593 nor OFQ had any effect. ME significantly decreased the frequency of spontaneous miniature EPSCs (mEPSCs) without change in their amplitude. The action of ME was mimicked by DAMGO. DPDPE had no effect. The presynaptic voltage-dependent potassium conductance blocker 4-aminopyridine (4-AP, 100 μM) abolished the inhibitory effects of ME on evoked IPSCs and EPSCs. In contrast, 4-AP only partially blocked the actions of baclofen. These results suggest that opioids inhibit inhibitory synaptic transmission in the STN through the activation of presynaptic μ- and δ-receptors. In contrast, inhibition of excitatory synaptic inputs to the STN occurs through the activation of only μ-receptors. Both inhibitions may be mediated by blockade of voltage-dependent potassium conductance.

AB - Presynaptic modulation of synaptic transmission in rat subthalamic nucleus (STN) neurons was investigated using whole-cell patch-clamp recordings in brain slices. Evoked GABAergic inhibitory postsynaptic currents (IPSCs) were reversibly reduced by methionine enkephalin (ME) with an IC50 value of 1.1 ± 0.3 μM. The action of ME was mimicked by the μ-selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), and was partially blocked by the μ-selective antagonists naloxonazine and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Evoked GABAA IPSCs were also inhibited by the δ-selective agonist [D-Pen2,5] -enkephalin (DPDPE), but not by the κ-selective agonist (+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl) -1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) and the orphan receptor agonist orphanin FQ/nociceptin (OFQ). DPDPE-induced inhibition was completely blocked by the δ-selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864). ME, DAMGO and DPDPE increased the paired-pulse ratio of IPSCs. Evoked excitatory postsynaptic currents (EPSCs) were reversibly reduced by ME with an IC50 value of 0.35 ± 0.14 μM. Inhibition by ME was associated with an increase in the paired-pulse ratio of EPSCs. The action of ME was mimicked by DAMGO, and blocked by naloxonazin. DPDPE had little effect on evoked EPSCs. Neither U-69593 nor OFQ had any effect. ME significantly decreased the frequency of spontaneous miniature EPSCs (mEPSCs) without change in their amplitude. The action of ME was mimicked by DAMGO. DPDPE had no effect. The presynaptic voltage-dependent potassium conductance blocker 4-aminopyridine (4-AP, 100 μM) abolished the inhibitory effects of ME on evoked IPSCs and EPSCs. In contrast, 4-AP only partially blocked the actions of baclofen. These results suggest that opioids inhibit inhibitory synaptic transmission in the STN through the activation of presynaptic μ- and δ-receptors. In contrast, inhibition of excitatory synaptic inputs to the STN occurs through the activation of only μ-receptors. Both inhibitions may be mediated by blockade of voltage-dependent potassium conductance.

UR - http://www.scopus.com/inward/record.url?scp=0037095914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037095914&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2001.013404

DO - 10.1113/jphysiol.2001.013404

M3 - Article

C2 - 12015431

AN - SCOPUS:0037095914

VL - 541

SP - 219

EP - 230

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 1

ER -