GABAergic modulation of D-1 dopamine receptor-mediated 3H-acetylcholine release from rabbit retina

J. G. Hensler, M. L. Dubocovich

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Dopamine evokes calcium-dependent release of 3H-acetylcholine from superfused rabbit retina labeled in vitro with 3H-choline, through activation of a D-1 dopamine receptor. This study investigates the activation of this receptor by endogenous dopamine and the modulation of the spontaneous and dopamine-evoked release of 3H-acetylcholine from rabbit retina labeled with 3H-choline by GABAergic agonists and antagonists. Endogenous dopamine, released from dopaminergic amacrine neurons by the indirect amines tyramine or D-amphetamine evoked the calcium-dependent release of 3H-acetylcholine from rabbit retina. The release of 3H-acetylcholine elicited by tyramine (10 μM) or D-amphetamine (10 μM) was attenuated by the selective D-1 antagonist SCH 23390 (0.1 μM) and by the dopamine uptake inhibitor nomifensine (3 μM). At concentrations of 1 mM and 1 μM respectively, GABA and muscimol inhibited the spontaneous release of tritium from rabbit retina labeled in vitro with 3H-choline. Picrotoxin and bicuculline (10 μM) increased the spontaneous release of tritium. GABA and the GABA agonist muscimol (0.01-100 μM) inhibited in a concentration-dependent manner the release of 3H-acetylcholine elicited by 100 μM dopamine with IC50 values of 4.5 μM and 0.02 μM respectively. The inhibition of dopamine-evoked 3H-acetylcholine release by GABA (10 μM) and muscimol (0.1 μM) was antagonized by the GABA antagonists bicuculline and picrotoxin. Picrotoxin and bicuculline (10 μM) increased the spontaneous release of tritium, and potentiated the release of 3H-acetylcholine evoked by 100 μM dopamine consistant with a tonic, inhibitory GABAergic input to the cholinergic amacrine neurons in rabbit retina. Dopamine-evoked acetylcholine release in rabbit retina may be of physiological importance as D-1 dopamine receptor-mediated increases in 3H-acetylcholine release from rabbit retina can be elicited by endogenous dopamine. In addition, activation of GABA receptor sites modulates the spontaneous and dopamine-evoked acetylcholine release from rabbit retina.

Original languageEnglish (US)
Pages (from-to)661-668
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume337
Issue number6
DOIs
StatePublished - Jun 1988

Keywords

  • D-1 dopamine receptor
  • GABA
  • H-acetylcholine release
  • Rabbit retina

ASJC Scopus subject areas

  • Pharmacology

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