Rat brain cortex slices preincubated with 3H-serotonin were superfused with physiological salt solution (containing citalopram, an inhibitor of serotonin uptake) and the effect of histamine on the electrically (3 Hz) evoked 3H overflow was studied. Histamine decreased the evoked overflow in a concentration-dependent manner. The inhibitory effect of histamine was antagonized by impromidine and burimamide, but was not affected by pheniramine, ranitidine, metitepine and phentolamine. Given alone, impromidine facilitated the evoked overflow, whereas burimamide, pheniramine and ranitidine had no effect. The results suggest that histamine inhibits serotonin release in the rat brain cortex via histamine H3 receptors, which may be located presynaptically.
Pig brain cortex synaptosomes and slices preincubated with 3H-5-hydroxytryptamine (3H-5-HT) were superfused with physiological salt solution containing citalopram (an inhibitor of 5-HT uptake), and the effects of indolethylamines and 5-HT receptor antagonists on the potassium- or electrically evoked 3H overflow were determined. The potassium (25 mmol/l)-evoked tritium overflow from cortex synaptosomes was inhibited by 5-HT; the inhibitory effect of 5-HT was counteracted by metitepine, which, by itself, did not affect the evoked overflow. 5-Methoxytryptamine (examined in the absence of citalopram) also produced an inhibition of the evoked overflow. In cortex slices, the electrically (3 Hz) evoked overflow was inhibited by 5-HT and 5-carboxamidotryptamine. The inhibitory effect of 5-HT was antagonized by metitepine, which, given alone, increased the evoked overflow, but was not attenuated by ketanserin and ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester), which, by themselves, did not influence the evoked overflow. The present results suggest that the serotoninergic nerve fibres of the pig brain cortex are endowed with presynaptic 5-HT1 receptors, which can be activated by endogenous and exogenous 5-HT.
The effect of RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1 H-indole) on the electrically evoked 3H overflow was studied in superfused rat brain cortex slices preincubated with 3H-noradrenaline or 3H-serotonin and in superfused segments of the rat vena cava preincubated with 3H-noradrenaline. In cortex slices preincubated with 3H-noradrenaline, RU 24969 facilitated the electrically (3 Hz) evoked 3H overflow. This effect was abolished by phentolamine but was not affected by desipramine or the 5-HT3 receptor antagonist ICS 205-930. The concentration-response curve of noradrenaline for its inhibitory effect on the evoked overflow (determined in the presence of desipramine) was shifted to the right by RU 24969 32 and 100 mumol/l. In this respect, RU 24969 was about 500 times less potent than phentolamine. In cortex slices preincubated with 3H-serotonin, the inhibitory effect of 3.2 mumol/l RU 24969 on the electrically evoked 3H overflow was increased by phentolamine. In segments of the vena cava, RU 24969 inhibited the electrically (0.66 Hz) evoked 3H overflow. The concentration-response curve of RU 24969 was U-shaped, since at concentrations higher than 0.1 mumol/l the extent of inhibition decreased with increasing concentrations of RU 24969. In the presence of phentolamine, the concentration-dependent attenuation of the RU 24969-induced inhibition of overflow was no longer detectable. The present results suggest that RU 24969 is a weak antagonist at presynaptic alpha 2-adrenoceptors (by more than 2.5 log units less potent than as an agonist at presynaptic 5-HT1B auto- and heteroreceptors).
Schlicker, E., R. Betz and M. Gothert: Vinpocetine facilitates noradrenaline release in rat brain cortex slices. Drug Dev. Res. 14:285-291, 1988. Rat brain cortex slices preincubated with ,H-noradrenaline were superfused with physiological salt solution, and the effect of vinpocetine on the electrically (3 Hz) evoked overflow was studied. Vinpocetine at 10-1 00 pmoliliter facilitated the evoked overflow: at 32 and 100 pmoliliter, basal efflux was slightly increased. The facilitatory effect of vinpocetine on the evoked overflow was not altered by desipramine, rolipram (an inhibitor of cAMP phosphodiesterase), or ICS ([3a-tropanyll-1 H-indole-3-carboxylic acid ester; an antagonist at 5-HT3 (M) receptors); it was strongly attenuated by phentolamine. In turn, vinpocetine moderately decreased the facilitatory effect of phentolamine on the evoked overflow. The concentrationresponse curve of noradrenaline (obtained in the presence of desipramine) for its inhibitory effect on the evoked overflow was not shifted to the right by vinpocetine at 32 and 100 pmoliliter. The present results show that vinpocetine facilitates noradrenaline release. This effect may be related to the blockade of presynaptic a,-adrenoceptors (although evidence is not unequivocal), but does not appear to involve inhibition of noradrenaline uptake or cAMP phosphodiesterase nor activation of 5-HT3 (M) receptors. The facilitatory effect of vinpocetine on noradrenaline release occurs at concentrations higher than those obtained under treatment with this drug.
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