Unique properties of norepinephrine release from terminals arising from the locus coeruleus: 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 [3H]NE release had steeper K+ dose-response curves than those observed for apparent hippocampal [3H]ACh, striatal [3H]DA and striatal [3H]5-HT release. In contrast, the apparent release of [3H]NE from the hypothalamus had a K+ dose-response curve similar to those observed for the release of [3H]ACh, [3H]DA and [3H]5-HT. Linopirdine, a drug which enhances K(+)-stimulated release of [3H]Ach, [3H]DA and [3H]5-HT, had no effect on cerebral cortical [3H]NE release even at submaximal K+ stimulation. Hippocampal [3H]NE release was also not affected by linopirdine, however the compound significantly enhanced K(+)-evoked [3H]NE release from hypothalamic slices. These data point to unique properties of [3H]NE release from terminals arising from the locus coeruleus (i.e. those found in the cerebral cortex and hippocampus) when compared to [3H]NE release from terminals derived from the lateral tegmentum (i.e. those found in the hypothalamus) and the release properties of other neurotransmitters. The relative high K+ sensitivity of NE release from coerulear terminals may be related to the lack of linopirdine effects on cerebral cortical and hippocampal [3H]NE release.
Zaczek
R
R
Central Nervous Systems Diseases Research, Du Pont Merck Pharmaceutical Company, Wilmington, DE.
Tinker
W J
WJ
Tam
S W
SW
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D007211:Indoles; D011725:Pyridines; D012701:Serotonin; C061017:linopirdine; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine