Effects of GABA, dopamine, and substance P on the release of newly synthesized 3H-5-hydroxytryptamine from rat substantia nigra in vitro.
The effects of GABA, substance P and dopamine on the release of newly synthesized 3H-5-HT were investigated, using slices of rat substantia nigra superfused with L-3H-tryptophan in vitro. GABA (50 micron) had no inhibitory effect on the potassium-evoked-release of 3H-5-HT. Substance P (50 micron) and eledoisin (50 micron) stimulated the spontaneous release of 3H-5-HT. This effect seems to be indirect and is possibly mediated by dopaminergic neurones, since the dopamine antagonist drug alpha-flupenthixol (1 micron) abolished the substance P-evoked release of 5-HT. Furthermore, it was found that substance P (10 micron) stimulated 3H-dopamine release from nigral slices in vitro and the dopaminergic agonist apomorphine (50 micron) also stimulated 3H-5-HT release. Substance P may, therefore, activate nigral dopaminergic neurones which then release dopamine from their dendrites. The release of dopamine may in turn stimulate 5-HT release from terminals of the raphe-nigral pathway.
D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D012701:Serotonin; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D004298:Dopamine