Schlicker E, Classen K, Göthert M
Institute of Pharmacology and Toxicology, University of Bonn, F.R.G.
J Cardiovasc Pharmacol. 1988 May;11(5):518-28. doi: 10.1097/00005344-198805000-00003.
Rat brain tissues preincubated with [3H]serotonin ([3H]5-HT) or [3H]norepinephrine ([3H]NE) were superfused in the presence of an inhibitor of serotonin or NE uptake, respectively. The electrically (3 Hz) evoked [3H]5-HT release from slices of the medulla oblongata [containing the nucleus tractus solitarii (NTS)] from Wistar rats was inhibited by 5-HT and NE, and these effects were counteracted by metitepine and phentolamine, respectively. The evoked [3H]5-HT release in slices from the cortex, medulla oblongata, and hypothalamus of 5-7-, 9-11-, and 19-22-week-old spontaneously hypertensive rats (SHR) did not differ from that in slices from age-matched Wistar-Kyoto rats (WKY). Nor was there any difference between strains for: the inhibitory effects of 5-HT and NE and the facilitatory effect of metitepine on the evoked [3H]5-HT release; the shift to the right of the concentration-response curves of 5-HT and NE by metitepine and phentolamine, respectively; the potassium (12 mM)-evoked [3H]5-HT release from cortex synaptosomes and its inhibition by 5-HT; the electrically evoked [3H]NE release in cortex slices, its inhibition by NE, and the shift to the right of the concentration-response curve of NE by phentolamine. The results provide evidence that 5-HT release in the rat brain NTS can be inhibited by 5-HT receptors and alpha-adrenoceptors. 5-HT release and its modulation by presynaptic 5-HT1 receptors and alpha 2-adrenoceptors as well as NE release and its modulation by presynaptic alpha 2-adrenoceptors do not differ between SHR and WKY rats. It may be of therapeutic relevance that according to these results the effects of 5-HT1 receptor agonists activating presynaptic 5-HT autoreceptors are not attenuated in this type of hypertension. It has been suggested that such agonists can be developed as a new class of antihypertensive drugs.
用[3H]血清素（[3H]5-HT）或[3H]去甲肾上腺素（[3H]NE）预孵育的大鼠脑组织，分别在存在血清素或NE摄取抑制剂的情况下进行灌流。电刺激（3Hz）诱发的Wistar大鼠延髓切片（含孤束核（NTS））中[3H]5-HT的释放受到5-HT和NE的抑制，且这些作用分别被美替平（metitepine）和酚妥拉明抵消。5-7周龄、9-11周龄和19-22周龄自发性高血压大鼠（SHR）的皮质、延髓和下丘脑切片中诱发的[3H]5-HT释放与年龄匹配的Wistar-Kyoto大鼠（WKY）切片中的释放无差异。在以下方面品系间也无差异：5-HT和NE的抑制作用以及美替平对诱发的[3H]5-HT释放的促进作用；美替平和酚妥拉明分别使5-HT和NE的浓度-反应曲线右移；钾（12mM）诱发的皮质突触体中[3H]5-HT的释放及其被5-HT抑制；皮质切片中电刺激诱发的[3H]NE释放、其被NE抑制以及酚妥拉明使NE的浓度-反应曲线右移。结果表明，大鼠脑NTS中的5-HT释放可被5-HT受体和α-肾上腺素能受体抑制。SHR和WKY大鼠之间，5-HT释放及其由突触前5-HT1受体和α2-肾上腺素能受体的调节以及NE释放及其由突触前α2-肾上腺素能受体的调节无差异。根据这些结果，5-HT1受体激动剂激活突触前5-HT自身受体的作用在这类高血压中未减弱，这可能具有治疗相关性。有人提出这类激动剂可被开发为一类新型抗高血压药物。
