Cholinergic nerve terminals of human cerebral cortex possess a GABA transporter whose activation induces release of acetylcholine.
The effect of gamma-aminobutyric acid (GABA) on the release of [3H]acetylcholine [( 3H]ACh) from human cerebral cortex nerve terminals was investigated using synaptosomes prepared from neurosurgical specimens (which had to be removed to reach deeply located tumors) prelabeled with [3H]choline and exposed in superfusion to varying concentrations of GABA. The amino acid (3-100 microM) increased in a concentration-dependent manner (maximal effect: 40%; EC50 = 14.7 microM) the release of [3H]ACh but not that of [3H]choline. The GABAA receptor agonist muscimol (up to 100 microM) did not increase significantly the release of [3H]ACh. Accordingly, the effect of GABA was insensitive to the GABAA receptor antagonist bicuculline. The release of [3H]ACh was not affected by the GABAB receptor agonist (-)-baclofen (100-300 microM). The GABA-induced [3H]ACh release was counteracted by two inhibitors of GABA uptake, N-(4,4-diphenyl-3-butenyl)nipecotic acid (SKF 89976A) and nipecotic acid. Moreover, the enhancing effect of GABA on [3H]ACh release was clearly Na+-dependent and was reduced by almost 90% in presence of 23 mM NaCl. The data indicate that, similarly to what had been observed in the rat, cholinergic nerve terminals in the human cerebral cortex possess a GABA transporter. Activation of this carrier brings about release of newly synthesized ACh. GABA and ACh might co-exist in some cerebrocortical nerve endings in the vertebrate brain, including man.
Bonanno
G
G
Instituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Ruelle
A
A
Andrioli
G C
GC
Raiteri
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000927:Anticonvulsants / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001711:Biotransformation; D002352:Carrier Proteins; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009118:Muscimol / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009557:Nipecotic Acids / Q000494:pharmacology; D027361:Organic Anion Transporters; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D000927:Anticonvulsants; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; C030278:nipecotic acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D011392:Proline; C010983:homoproline; D001418:Baclofen; D002794:Choline; D000109:Acetylcholine; D001640:Bicuculline