Nitric oxide participates in the stimulatory and neurotoxic action of endothelin on rat striatal dopaminergic neurons.
1. Our method of real-time monitoring of dopamine release from rat striatal slices revealed that endothelin (ET)-3-induced dopamine release was inhibited by NG-methyl-L-arginine (L-NMMA; 1 mM), an inhibitor of nitric oxide (NO) synthase, while NG-methyl-D-arginine (D-NMMA; 1 mM), an inactive isomer of L-NMMA, had no effect. 2. The inhibition of L-NMMA (0.1 mM) became apparent when tissues were pretreated with tetrodotoxin (1 microM) for 30 min and subsequently exposed to ET-3 (4 microM). 3. L-NMMA (0.1 and 1 mM) dose dependently protected against ET-3-triggered hypoxic/hypoglycemic impairment of striatal responses to high K+. 4. Thus, NO may work as a promoter in mediation of the stimulatory and neurotoxic action of ET-3 on the striatal dopaminergic system, presumably by interacting with interneurons in the striatum.
Shibaguchi
H
H
Department of Biochemistry, Nagasaki University School of Medicine, Japan.
Kataoka
Y
Y
Koizumi
S
S
Kohzuma
M
M
Obana
M
M
Himeno
A
A
Yamashita
K
K
Taniyama
K
K
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D019334:Endothelin-3 / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007003:Hypoglycemia / Q000503:physiopathology; D007395:Interneurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009498:Neurotoxins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019334:Endothelin-3; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D011188:Potassium; D010100:Oxygen; D004298:Dopamine