Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx to produce biphasic dopamine release from rat striatal slices.
1. Real-time monitoring of dopamine (DA) release from rat striatal slices demonstrated that endothelin (ET)-3 (0.1-10 microM) produced a biphasic DA release consisting of transient and sustained components. When extracellular Ca2+ was removed, the sustained but not transient response remarkably decreased. 2. ET-3 (1-10 microM) stimulated an increase in the intracellular Ca2+ concentration ([Ca(2+)]i), which also consisted of two components. The external Ca2+ depletion inhibited primarily the sustained component of the Ca2+ response to ET-3. 3. ET-3 increased inositol 1,4,5-trisphosphate (IP3) concentrations in striatal slices. This response peaked at 10 to 20 sec and returned to the basal level 2 min after stimulation, an event which was in good accord with a prompt and transient phase of both cytosolic Ca2+ activity and DA release evoked by ET-3. 4. Thus, ET-3 produces a transient and a sustained release of DA from striatal slices by stimulating intracellular Ca2+ mobilization via IP3 formation and extracellular Ca2+ influx, respectively.
Kataoka
Y
Y
Department of Pharmacology 2, Nagasaki University School of Medicine, Japan.
Koizumi
S
S
Niwa
M
M
Shibaguchi
H
H
Shigematsu
K
K
Kudo
Y
Y
Taniyama
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018492:Dopamine Antagonists; D016232:Endothelins; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D004298:Dopamine