NITRIC-OXIDE PARTICIPATES IN THE STIMULATORY AND NEUROTOXIC ACTION OFENDOTHELIN ON RAT STRIATAL DOPAMINERGIC-NEURONS

1. Our method of real-time monitoring of dopamine release from rat str iatal slices revealed that endothelin (ET)-3-induced dopamine release was inhibited by N-G-methyl-L-arginine (L-NMMA; 1 mM), an inhibitor of nitric oxide (NO) synthase, while N-G-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 tetro dotoxin (1 mu M) for 30 min and subsequently exposed to ET-3 (4 mu M). 3. L-NMMA (0.1 and 1 mM) dose dependently protected against ET-3-trig gered hypoxic/hypoglycemic impairment of striatal responses to high K. 4. Thus, NO may work as a promoter in mediation of the stimulatory a nd neurotoxic action of ET-3 on the striatal dopaminergic system, pres umably by interacting with interneurons in the striatum.