Presynaptic Serotonin Receptors and α-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 or seotonin or NE uptake, respectively. The electrically (3 Hz) evoked [3H]-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 bt 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]-HT release from cortex synaptosomes and its inhibition by 5-HT; the electrically evoked [3H]NE release in cortex slices, in 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.