Endogenous noradrenaline as modulator of hippocampal serotonin (5-HT)-release. Dual effects of yohimbine, rauwolscine and corynanthine as alpha-adrenoceptor antagonists and 5-HT-receptor agonists.
The modulation of hippocampal serotonin (5-HT)-release by noradrenaline was studied in rabbit hippocampal slices, which were preincubated with 3H-serotonin and then superfused continuously. Electrical field stimulation of the slices elicited a tritium overflow, which was decreased by clonidine in a concentration dependent manner. Phentolamine antagonized the effects of clonidine and, given alone, increased the evoked tritium overflow. This facilitatory effect of phentolamine was further enhanced in the presence of (+)oxaprotilin, a highly selective noradrenaline uptake inhibitor, whereas the (-)enantiomer of oxaprotilin, which does not affect noradrenaline uptake, was inactive. (+)Oxaprotilin but not (-)oxaprotilin, given alone, inhibited the evoked tritium overflow. The inhibitory effect of (+)oxaprotilin was antagonized by phentolamine. In the presence of phentolamine, the alpha-adrenoceptor antagonists yohimbine, rauwolscine and corynanthine decreased the evoked 5-HT-release concentration dependently. Their inhibitory effects were, however, abolished (corynanthine) or inversed to a facilitation of release (yohimbine, rauwolscine) if instead of phentolamine the 5-HT-receptor antagonist metitepin was present. Therefore we suggest that yohimbine, rauwolscine and corynanthine, in addition to their alpha-adrenoceptor antagonistic properties, may act as agonists at 5-HT-autoreceptors. Possibly the indol part of their molecules is responsible for this effect. Furthermore, our results provide evidence for the modulation of hippocampal 5-HT-release by endogenous noradrenaline.
Feuerstein
T J
TJ
Hertting
G
G
Jackisch
R
R
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D008376:Maprotiline; D015016:Yohimbine; D012701:Serotonin; C027299:hydroxymaprotilin; D003000:Clonidine; D009638:Norepinephrine; D010646:Phentolamine