Premium
Coexistence of carriers for dopamine and GABA uptake on a same nerve terminal in the rat brain
Author(s) -
Bonanno Giambattista,
Raiteri Maurizio
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb09004.x
Subject(s) - dopamine , nipecotic acid , muscimol , chemistry , bicuculline , medicine , endocrinology , picrotoxin , agonist , striatum , gaba receptor antagonist , neurotransmitter , gabaa receptor , biology , receptor , biochemistry
1 The ability of γ‐aminobutyric acid (GABA) to affect the release of [ 3 H]‐dopamine in rat brain synaptosomes prepared from corpus striatum, frontal cortex and hypothalamus and prelabelled with the radioactive catecholamine in the presence of desipramine was examined. 2 GABA (10–300 μ m ) increased in a concentration‐dependent way the basal release of [ 3 H]‐dopamine from striatum and cortical synaptosomes; however, its effect was much less pronounced in hypothalamic nerve terminals. 2,4‐Diaminobutyric acid (DABA) mimicked GABA although less potently. 3 Neutral amino acids such as leucine, valine or α‐aminoisobutyric acid (100–300 μ m ) did not affect or increased minimally the release of [ 3 H]‐dopamine. 4 The GABA‐induced [ 3 H]‐dopamine release was not prevented by the GABA A ‐receptor antagonists, bicuculline or picrotoxin. The GABA A ‐receptor agonist, muscimol (10–300 μ m ), displayed only a very weak, not significant, enhancing effect on [ 3 H]‐dopamine release. The GABA B ‐receptor agonist (—)‐ baclofen (100 or 300 μ m ) had no effect. 5 Three novel and selective inhibitors of GABA uptake, N‐(4,4‐diphenyl‐3‐butenyl)‐nipecotic acid (SK&F 89976A), N‐(4,4‐diphenyl‐3‐butenyl)‐guvacine (SK&F 100330A) and N‐(4,4‐diphenyl‐3‐butenyl)‐homo‐β‐proline (SK&F 100561) potently counteracted the enhancing effect of GABA on [ 3 H]‐dopamine release. Nipecotic acid also reduced the effect of GABA. 6 It is concluded that carriers for the uptake of dopamine and GABA may coexist on the same nerve terminal in the rat brain.