How opioids inhibit GABA-mediated neurotransmission

C. W. Vaughan, Susan Ingram, M. A. Connor, M. J. Christie

Research output: Contribution to journalArticle

389 Citations (Scopus)

Abstract

The midbrain region periaqueductal grey (PAG) is rich in opioid receptors and endogenous opioids and is a major target of analgesic action in the central nervous system. It has been proposed that the analgesic effect of opioids on the PAG works by suppressing the inhibitory influence of the neurotransmitter GABA (γ-aminobutyric acid) on neurons that form part of a descending antinociceptive pathway. Opioids inhibit GABA-mediated (GABAergic) synaptic transmission in the PAG and other brain regions by reducing the probability of presynaptic neurotransmitter release, but the mechanisms involved remain uncertain. Here we report that opioid inhibition of GABAergic synaptic currents in the PAG is controlled by a presynaptic voltage-dependent potassium conductance. Opioid receptors of the μ type in GABAergic presynaptic terminals are specifically coupled to this potassium conductance by a pathway involving phospholipase A2, arachidonic acid and 12- lipoxygenase. Furthermore, opioid inhibition of GABAergic synaptic transmission is potentiated by inhibitors of the enzymes cyclooxygenase and 5-lipoxygenase, presumably because more arachidonic acid is available for conversion to 12-lipoxygenase products. These mechanisms account for the analgesic action of cyclooxygenase inhibitors in the PAG and their synergism with opioids.

Original languageEnglish (US)
Pages (from-to)611-614
Number of pages4
JournalNature
Volume390
Issue number6660
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Periaqueductal Gray
Synaptic Transmission
gamma-Aminobutyric Acid
Opioid Analgesics
Arachidonate 12-Lipoxygenase
Cyclooxygenase Inhibitors
Opioid Receptors
Neurotransmitter Agents
Analgesics
Potassium
Aminobutyrates
Arachidonate 5-Lipoxygenase
Phospholipases A2
Presynaptic Terminals
Enzyme Inhibitors
Mesencephalon
Arachidonic Acid
Central Nervous System
Neurons
Brain

ASJC Scopus subject areas

  • General

Cite this

Vaughan, C. W., Ingram, S., Connor, M. A., & Christie, M. J. (1997). How opioids inhibit GABA-mediated neurotransmission. Nature, 390(6660), 611-614. https://doi.org/10.1038/37610

How opioids inhibit GABA-mediated neurotransmission. / Vaughan, C. W.; Ingram, Susan; Connor, M. A.; Christie, M. J.

In: Nature, Vol. 390, No. 6660, 1997, p. 611-614.

Research output: Contribution to journalArticle

Vaughan, CW, Ingram, S, Connor, MA & Christie, MJ 1997, 'How opioids inhibit GABA-mediated neurotransmission', Nature, vol. 390, no. 6660, pp. 611-614. https://doi.org/10.1038/37610
Vaughan CW, Ingram S, Connor MA, Christie MJ. How opioids inhibit GABA-mediated neurotransmission. Nature. 1997;390(6660):611-614. https://doi.org/10.1038/37610
Vaughan, C. W. ; Ingram, Susan ; Connor, M. A. ; Christie, M. J. / How opioids inhibit GABA-mediated neurotransmission. In: Nature. 1997 ; Vol. 390, No. 6660. pp. 611-614.
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