Glycine stimulates the release of labeled acetylcholine but not dopamine nor glutamate from superfused rat striatal tissue.
Glycine is known as an inhibitory neurotransmitter in the spinal cord and forebrain but its precise role in the forebrain is largely overlooked. This investigation evaluated whether glycine alters acetylcholine, glutamate or dopamine release from striatal tissue using an in vitro approach. We observed that while glycine induced a robust (3)H-acetylcholine release ((3)H-ACh) from superfused striatal tissue, it failed at releasing (3)H-glutamate or (3)H-dopamine. Glycine stimulated (3)H-ACh release in a dose- and calcium-dependent manner (EC(50)=69 microM). Tetrodotoxin (1 microM) inhibited about 75% of the release demonstrating a predominant dendritic and cell body location of glycine receptors. The prototypical glycine receptor antagonist strychnine at 10 microM completely abolished (3)H-ACh release. To further characterize the role of striatal glycine receptors in (3)H-ACh release we examined glycine effects after in vivo treatment with Haloperidol-decanoate (HD). Treatment for 30 days or more with HD decreased maximal glycine-stimulated release of (3)H-ACh suggesting a non-competitive inhibition. After 30 days of washout release parameters did not return to vehicle-treated levels. The glutamate agonist NMDA also stimulated acetylcholine release but showed slightly different behavior in HD-treated striatal tissue. These effects could be attributed to changes in chloride transporters expressed in the giant striatal cholinergic cell as well as glycine receptor subunit composition and finally, GABA/glycine co-release in this tissue.
Hernandes
Marina Sorrentino
MS
Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503.900, Brazil.
de Magalhães
Leandro
L
Troncone
Lanfranco Ranieri Paolo
LR
D000109:Acetylcholine / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D005998:Glycine / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology*; D006220:Haloperidol / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D018684:Glycine Agents; D026941:Sodium Channel Blockers; D014316:Tritium; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; C033563:haloperidol decanoate; D006220:Haloperidol; D000109:Acetylcholine; D002118:Calcium; D005998:Glycine; D004298:Dopamine