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.
Koizumi
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kataoka
Y
Y
Niwa
M
M
Watanabe
S
S
Taniyama
K
K
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