UNIQUE PROPERTIES OF NOREPINEPHRINE RELEASE FROM TERMINALS ARISING FROM THE LOCUS-CERULEUS - HIGH POTASSIUM SENSITIVITY AND LACK OF LINOPIRDINE (DUP-996) ENHANCEMENT

The dose-response of K+ to elicit the release of norepinephrine (NE), acetylcholine (ACh), dopamine (DA) and serotonin (5-HT) from rat brain slices was examined. Cerebral cortical and hippocampal [H-3]NE releas e had steeper K+ dose-response curves than those observed for apparent hippocampal [H-3]ACh, striatal [H-3]DA and striatal [H-3]5-HT release . In contrast, the apparent release of [H-3]NE from the hypothalamus h ad a K+ dose-response curve similar to those observed for the release of [H-3]ACh, [H-3]DA and [H-3]5-HT. Linopirdine, a drug which enhances K+-stimulated release of [H-3]ACh, [H-3]DA and [H-3]5-HT, had no effe ct on cerebral cortical [H-3]NE release even at submaximal K+ stimulat ion. Hippocampal [H-3]NE release was also not affected by linopirdine, however the compound significantly enhanced K+-evoked [H-3]NE release from hypothalamic slices. These data point to unique properties of [H -3]NE release from terminals arising from the locus coeruleus (i.e. th ose found in the cerebral cortex and hippocampus) when compared to [H- 3]NE release from terminals derived from the lateral tegmentum (i.e. t hose found in the hypothalamus) and the release properties of other ne urotransmitters. The relative high K+ sensitivity of NE release from c oerulear terminals may be related to the lack of linopirdine effects o n cerebral cortical and hippocampal [H-3]NE release.