D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea

G. Halmos, Z. Doleviczényi, G. Répássy, A. Kittel, E. Vízi, B. Lendvai, T. Zelles

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Dopamine (DA), released from the lateral olivocochlear (LOC) efferent terminals, the efferent arm of the short-loop feedback in the cochlea, is considered as a protective factor in the inner ear since it inhibits auditory nerve dendrite firing in ischemia- or noise-induced excitotoxicity leading to sensorineural hearing loss (SNHL). In the present study we investigated the effect of oxygen-glucose deprivation (OGD), an in vitro ischemia model, on guinea-pig cochlear [3H]DA release in a microvolume superfusion system. We found that OGD alone failed to induce a detectable elevation of [3H]DA level, but in the presence of specific D2 receptor antagonists, sulpiride and L-741,626, it evoked a significant increase in the extracellular concentration of [3H]DA. D2 negative feedback receptors are involved not exclusively in the regulation of synthesis and vesicular release of DA, but also in the activation of its reuptake. Thus, D2 receptor antagonism interferes with the powerful reuptake of DA from the extracellular space. To explore the underlying mechanism of this DA-releasing effect we applied nomifensine and found that the effect of OGD on cochlear DA release in the presence of D2 antagonists could be inhibited by this selective DA uptake inhibitor. This finding indicates that the OGD-evoked DA release was mainly mediated through the reverse operation of the DA transporter. The two structurally different D2 antagonists also augmented the electrical field stimulation-evoked release of DA proving the presence of D2 autoreceptors on dopaminergic LOC terminals. Our results confirm the presence and role of D2 DA autoreceptors in the regulation of DA release from LOC efferents, and suggest a protective local mechanism during ischemia which involves the direct transporter-mediated release of DA. Increasing the release of the protective transmitter DA locally in the inner ear may form the basis of future new therapeutic strategies in patients suffering from SNHL.

Original languageEnglish
Pages (from-to)801-809
Number of pages9
JournalNeuroscience
Volume132
Issue number3
DOIs
Publication statusPublished - 2005

Fingerprint

Autoreceptors
Cochlea
Dopamine
Guinea Pigs
Oxygen
Glucose
Ischemia
Sensorineural Hearing Loss
Inner Ear
3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole
Dopamine Uptake Inhibitors
Nomifensine
Sulpiride
Cochlear Nerve
Dopamine Agents
Dopamine Plasma Membrane Transport Proteins
Extracellular Space
Dendrites
Electric Stimulation
Noise

Keywords

  • Cochlea
  • D autoreceptor
  • Dopamine release
  • Ischemia
  • Oxygen-glucose deprivation
  • Transporter

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea. / Halmos, G.; Doleviczényi, Z.; Répássy, G.; Kittel, A.; Vízi, E.; Lendvai, B.; Zelles, T.

In: Neuroscience, Vol. 132, No. 3, 2005, p. 801-809.

Research output: Contribution to journalArticle

@article{397ca8ffb17940bc9f267e21da8cb1e9,
title = "D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea",
abstract = "Dopamine (DA), released from the lateral olivocochlear (LOC) efferent terminals, the efferent arm of the short-loop feedback in the cochlea, is considered as a protective factor in the inner ear since it inhibits auditory nerve dendrite firing in ischemia- or noise-induced excitotoxicity leading to sensorineural hearing loss (SNHL). In the present study we investigated the effect of oxygen-glucose deprivation (OGD), an in vitro ischemia model, on guinea-pig cochlear [3H]DA release in a microvolume superfusion system. We found that OGD alone failed to induce a detectable elevation of [3H]DA level, but in the presence of specific D2 receptor antagonists, sulpiride and L-741,626, it evoked a significant increase in the extracellular concentration of [3H]DA. D2 negative feedback receptors are involved not exclusively in the regulation of synthesis and vesicular release of DA, but also in the activation of its reuptake. Thus, D2 receptor antagonism interferes with the powerful reuptake of DA from the extracellular space. To explore the underlying mechanism of this DA-releasing effect we applied nomifensine and found that the effect of OGD on cochlear DA release in the presence of D2 antagonists could be inhibited by this selective DA uptake inhibitor. This finding indicates that the OGD-evoked DA release was mainly mediated through the reverse operation of the DA transporter. The two structurally different D2 antagonists also augmented the electrical field stimulation-evoked release of DA proving the presence of D2 autoreceptors on dopaminergic LOC terminals. Our results confirm the presence and role of D2 DA autoreceptors in the regulation of DA release from LOC efferents, and suggest a protective local mechanism during ischemia which involves the direct transporter-mediated release of DA. Increasing the release of the protective transmitter DA locally in the inner ear may form the basis of future new therapeutic strategies in patients suffering from SNHL.",
keywords = "Cochlea, D autoreceptor, Dopamine release, Ischemia, Oxygen-glucose deprivation, Transporter",
author = "G. Halmos and Z. Dolevicz{\'e}nyi and G. R{\'e}p{\'a}ssy and A. Kittel and E. V{\'i}zi and B. Lendvai and T. Zelles",
year = "2005",
doi = "10.1016/j.neuroscience.2005.01.023",
language = "English",
volume = "132",
pages = "801--809",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea

AU - Halmos, G.

AU - Doleviczényi, Z.

AU - Répássy, G.

AU - Kittel, A.

AU - Vízi, E.

AU - Lendvai, B.

AU - Zelles, T.

PY - 2005

Y1 - 2005

N2 - Dopamine (DA), released from the lateral olivocochlear (LOC) efferent terminals, the efferent arm of the short-loop feedback in the cochlea, is considered as a protective factor in the inner ear since it inhibits auditory nerve dendrite firing in ischemia- or noise-induced excitotoxicity leading to sensorineural hearing loss (SNHL). In the present study we investigated the effect of oxygen-glucose deprivation (OGD), an in vitro ischemia model, on guinea-pig cochlear [3H]DA release in a microvolume superfusion system. We found that OGD alone failed to induce a detectable elevation of [3H]DA level, but in the presence of specific D2 receptor antagonists, sulpiride and L-741,626, it evoked a significant increase in the extracellular concentration of [3H]DA. D2 negative feedback receptors are involved not exclusively in the regulation of synthesis and vesicular release of DA, but also in the activation of its reuptake. Thus, D2 receptor antagonism interferes with the powerful reuptake of DA from the extracellular space. To explore the underlying mechanism of this DA-releasing effect we applied nomifensine and found that the effect of OGD on cochlear DA release in the presence of D2 antagonists could be inhibited by this selective DA uptake inhibitor. This finding indicates that the OGD-evoked DA release was mainly mediated through the reverse operation of the DA transporter. The two structurally different D2 antagonists also augmented the electrical field stimulation-evoked release of DA proving the presence of D2 autoreceptors on dopaminergic LOC terminals. Our results confirm the presence and role of D2 DA autoreceptors in the regulation of DA release from LOC efferents, and suggest a protective local mechanism during ischemia which involves the direct transporter-mediated release of DA. Increasing the release of the protective transmitter DA locally in the inner ear may form the basis of future new therapeutic strategies in patients suffering from SNHL.

AB - Dopamine (DA), released from the lateral olivocochlear (LOC) efferent terminals, the efferent arm of the short-loop feedback in the cochlea, is considered as a protective factor in the inner ear since it inhibits auditory nerve dendrite firing in ischemia- or noise-induced excitotoxicity leading to sensorineural hearing loss (SNHL). In the present study we investigated the effect of oxygen-glucose deprivation (OGD), an in vitro ischemia model, on guinea-pig cochlear [3H]DA release in a microvolume superfusion system. We found that OGD alone failed to induce a detectable elevation of [3H]DA level, but in the presence of specific D2 receptor antagonists, sulpiride and L-741,626, it evoked a significant increase in the extracellular concentration of [3H]DA. D2 negative feedback receptors are involved not exclusively in the regulation of synthesis and vesicular release of DA, but also in the activation of its reuptake. Thus, D2 receptor antagonism interferes with the powerful reuptake of DA from the extracellular space. To explore the underlying mechanism of this DA-releasing effect we applied nomifensine and found that the effect of OGD on cochlear DA release in the presence of D2 antagonists could be inhibited by this selective DA uptake inhibitor. This finding indicates that the OGD-evoked DA release was mainly mediated through the reverse operation of the DA transporter. The two structurally different D2 antagonists also augmented the electrical field stimulation-evoked release of DA proving the presence of D2 autoreceptors on dopaminergic LOC terminals. Our results confirm the presence and role of D2 DA autoreceptors in the regulation of DA release from LOC efferents, and suggest a protective local mechanism during ischemia which involves the direct transporter-mediated release of DA. Increasing the release of the protective transmitter DA locally in the inner ear may form the basis of future new therapeutic strategies in patients suffering from SNHL.

KW - Cochlea

KW - D autoreceptor

KW - Dopamine release

KW - Ischemia

KW - Oxygen-glucose deprivation

KW - Transporter

UR - http://www.scopus.com/inward/record.url?scp=17044429374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17044429374&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2005.01.023

DO - 10.1016/j.neuroscience.2005.01.023

M3 - Article

VL - 132

SP - 801

EP - 809

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -