CA2+-DEPENDENT AND CA2+-INDEPENDENT MECHANISMS OF ISCHEMIA-EVOKED RELEASE OF [H-3] DOPAMINE FROM RAT STRIATAL SLICES

1. Ischaemia was induced by 5 min of deprivation of glucose and an additional 5 min of deprivation of glucose and oxygen from Mg2+-free artificial cerebrospinal fluid in vitro. 2. During the ischaemic period, 11 +/- 1.5% of the total [H-3]-dopamine ([H-3]-DA) was released into the incubation medium. 3. Ischaemia-evoked release of [H-3]-DA from striatal slices was attenuated by tetrodotoxin (TTX), MgSO4, dizocilpine, ketamine, 6,7-dinitroquinoxaline-2,3-dione (DNQX), or carbetapentane. 4. Release of PHI-DA was attenuated by verapamil, omega-conotoxin GVIA and dantrolene. 5. Nomifensin inhibited the ischaemia-induced release of [H-3]-DA. 6. Omission of Ca2+ from incubation media potentiated ischaemia-evoked [H-3]-DA release. The inhibitory effect of nomifensin was potentiated in Ca2+-free incubation media. 7. These results suggest that ischaemia induces release of [H-3]-DA by dual mechanisms; one is Ca2+-dependent exocytosis and the other is reversal of transporter.