Singewald N, Schneider C, Pfitscher A, Philippu A
Institut für Pharmakologie und Toxikologie, Universität Innsbruck, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):339-45. doi: 10.1007/BF00178948.
To investigate the release of endogenous dopamine, noradrenaline and adrenaline in the locus coeruleus, this brain area was superfused with artificial cerebrospinal fluid (CSF) through push-pull cannulae and the release of catecholamines was determined in the superfusate radioenzymatically. Collection of superfusates in time periods of 10 min revealed that release rates of the three catecholamines fluctuated, thus pointing to the existence of ultradian rhythms with following mean periods (minutes per cycle): noradrenaline 52 +/- 4, dopamine 37 +/- 2, adrenaline 36 +/- 2. The rhythm frequency of noradrenaline was significantly lower than the frequencies of dopamine and adrenaline. When the locus coeruleus was superfused with neuroactive drugs, superfusates were collected in time periods of 3 min. Superfusion with tetrodotoxin (1 mumol l-1) for 12 min elicited a prompt and sustained decrease (-70%) in the release rates of dopamine and adrenaline. The release rate of noradrenaline was also reduced, although to a lesser extent (-40%). Superfusion with veratridine (50 mumol l-1) led to an immediate and very pronounced enhancement in the release rates of dopamine, noradrenaline and adrenaline. The veratridine-induced increase in catecholamine outflow was decreased strongly by simultaneous superfusion with tetrodotoxin. The findings suggest that the release of endogenous catecholamines in the locus coeruleus fluctuates according to ultradian rhythms. Changes in the release on superfusion with veratridine and tetrodotoxin demonstrate the neuronal origin of the three catecholamines. The observed differences in the release characteristics between noradrenaline on the one hand and dopamine and adrenaline on the other might indicate that noradrenaline is partly released from somatodendritic sites of the noradrenergic cell bodies in the locus coeruleus.
为研究蓝斑核中内源性多巴胺、去甲肾上腺素和肾上腺素的释放情况,通过推挽式套管将该脑区用人工脑脊液(CSF)进行灌流,并采用放射酶法测定灌流液中儿茶酚胺的释放量。以10分钟为时间段收集灌流液,结果显示三种儿茶酚胺的释放速率存在波动,这表明存在超日节律,其平均周期如下(每分钟每周期):去甲肾上腺素52±4,多巴胺37±2,肾上腺素36±2。去甲肾上腺素的节律频率显著低于多巴胺和肾上腺素的频率。当用神经活性药物灌流蓝斑核时,以3分钟为时间段收集灌流液。用河豚毒素(1μmol/L)灌流12分钟可使多巴胺和肾上腺素的释放速率迅速且持续下降(-70%)。去甲肾上腺素的释放速率也有所降低,尽管降幅较小(-40%)。用藜芦碱(50μmol/L)灌流会导致多巴胺、去甲肾上腺素和肾上腺素的释放速率立即且显著增加。同时用河豚毒素灌流可强烈降低藜芦碱诱导的儿茶酚胺流出增加。这些发现表明,蓝斑核中内源性儿茶酚胺的释放随超日节律波动。用藜芦碱和河豚毒素灌流时释放的变化证明了这三种儿茶酚胺的神经元来源。观察到的去甲肾上腺素与多巴胺和肾上腺素之间释放特性的差异可能表明,去甲肾上腺素部分是从蓝斑核中去甲肾上腺素能细胞体的胞体树突部位释放的。