Two distinct pathways are involved in the endothelin-3-evoked dopamine release from rat striatal slices.
We investigated mechanisms mediating endothelin-3-evoked dopamine release from rat striatal slices. Endothelin-3 stimulated dopamine release from the slices in a concentration-dependent manner over a range from 1 to 10 microM. Tetrodotoxin suppressed dopamine release, but left 40% of the release unaffected. Nifedipine, a voltage-gated Ca2+ channel (VGCC) antagonist, significantly inhibited dopamine release in the presence and absence of tetrodotoxin. Endothelin-3-evoked dopamine release was attenuated by D-2-amino-5-phosphnovaleric acid or Mg2+, N-methyl-D-aspartate receptor inhibitors, and this attenuation was not observed in the presence of tetrodotoxin, thereby indicating that the tetrodotoxin-sensitive component of dopamine release was partially mediated by glutamatergic pathways. This view was also supported by findings that endothelin-3 evoked glutamate release and the exogenously applied glutamate stimulated dopamine release. Based on these results, we hypothesize that endothelin-3 produces dopamine release through two distinct mechanisms; one is a direct stimulation of dopaminergic nerve terminals and the other was activation of interneurons which promoted the release of glutamate, resulting in dopamine release.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
S
S
Koizumi
Y
Y
Kataoka
M
M
Niwa
S
S
Watanabe
K
K
Taniyama
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D016232:Endothelins / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D016232:Endothelins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D009543:Nifedipine; D004298:Dopamine