GABAergic modulation of D-1 dopamine receptor-mediated 3H-acetylcholine release from rabbit retina.
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 microM) or D-amphetamine (10 microM) was attenuated by the selective D-1 antagonist SCH 23390 (0.1 microM) and by the dopamine uptake inhibitor nomifensine (3 microM). At concentrations of 1 mM and 1 microM respectively, GABA and muscimol inhibited the spontaneous release of tritium from rabbit retina labeled in vitro with 3H-choline. Picrotoxin and bicuculline (10 microM) increased the spontaneous release of tritium. GABA and the GABA agonist muscimol (0.01-100 microM) inhibited in a concentration-dependent manner the release of 3H-acetylcholine elicited by 100 microM dopamine with IC50 values of 4.5 microM and 0.02 microM respectively. The inhibition of dopamine-evoked 3H-acetylcholine release by GABA (10 microM) and muscimol (0.1 microM) was antagonized by the GABA antagonists bicuculline and picrotoxin. Picrotoxin and bicuculline (10 microM) increased the spontaneous release of tritium, and potentiated the release of 3H-acetylcholine evoked by 100 microM dopamine consistent with a tonic, inhibitory GABAergic input to the cholinergic amacrine neurons in rabbit retina.(ABSTRACT TRUNCATED AT 250 WORDS)
Hensler
J G
JG
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Dubocovich
M L
ML
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000378:metabolism; D018756:GABA Antagonists; D066298:In Vitro Techniques; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects*; D012160:Retina / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D011954:Receptors, Dopamine; D005680:gamma-Aminobutyric Acid; D002794:Choline; D000109:Acetylcholine