Presynaptic serotonin receptors and alpha-adrenoceptors on central serotoninergic and noradrenergic neurons of normotensive and spontaneously hypertensive rats.
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.
Schlicker
E
E
Institute of Pharmacology and Toxicology, University of Bonn, F.R.G.
Classen
K
K
Göthert
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012701:Serotonin; D009638:Norepinephrine