Presynaptic serotonin receptors and alpha-adrenoceptors on central serotoninergic and noradrenergic neurons of normotensive and spontaneously hypertensive rats

Abstract

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.