| Abstrakt: |
In segments of human right atrial appendages preincubated with [3]noradrenaline and superfused with physiological salt solution containing desipramine and corticosterone, we determined the effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on tritium overflow evoked by transmural electrical stimulation (2 Hz). Tritium overflow was inhibited by 5-HT, 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-McOT), 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate (RU 24969) and sumatriptan. Yohimbine and oxymetazoline (in the presence of idazoxan) also inhibited tritium overflow. The inhibitory potency of the drugs was significantly correlated with their affinity for 5-HT receptors in human brain and for cloned human 5-HT and 5-HT receptors, but not with their affinity for 5HT, 5-HT, 5-HT, 5-HT, 5-HT, 5-HT, 5-HT, 5-HT, 5-HT and 5-HT receptors. The potency order 5-CT >5-HT >5-MeOT is opposite to the order of affinities reported for 5-HT binding sites. The preferential 5-HT receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (up to 0.3 μM) and the selective 5-HT receptor agonist cisapride (up to 1 μM) failed to inhibit tritium overflow. L-694,247, a potent 5-HT receptor agonist, did not inhibit tritium overflow, but counteracted the inhibitory effect of 5-HT. Ketanserin at a concentration which should block 5-HT but not 5-HT receptors and methiothepin at a concentration which may be assumed to block both 5-HT and 5-HT receptors antagonized the inhibitory effect of 5-HT. Propranolol and ondansetron did not modify the 5-HT-induced inhibition of release. In conclusion, noradrenaline release in human right atrial appendages is inhibited via 5-HT receptors which are located on the noradrenergic axon terminals. These inhibitory presynaptic 5-HT receptors belong to the 5-HT subfamily. The ability of ketanserin to antagonize the inhibitory effect induced by activation of these receptors suggests that they can be subclassified as 5-HT. [ABSTRACT FROM AUTHOR] |
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