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Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT1D subtype

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Summary

The human saphenous vein preincubated with [3H]noradrenaline was used to determine the pharmacological properties of the release-inhibiting presynaptic serotonin (5-HT) receptor on the sympathetic nerves. The overflow of tritium evoked by transmural electrical stimulation (2 Hz) was concentration-dependently inhibited by drugs known to stimulate 5-HT receptors in the following rank order: oxymetazoline ≥ 5-HT ≥ 5-carboxamidotryptamine = 5-methoxytryptamine = sumatriptan > tryptamine > N,N(CH3)2-5-HT = yohimbine = 8-hydroxy-2-(di-n-propylamino)-tetraline. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT1B and 5-HT1D binding sites, but not with those for 5-HT1A or 5-HT1C binding sites. 5-Aminotryptamine, methysergide, ipsapirone, cyanopindolol, SDZ 21009 and metergoline dit not produce a significant inhibition. Metitepine and methysergide antagonized the inhibitory effect of 5-HT, whereas spiroxatrine, propranolol, ketanserin and ICS 205-930 did not.

These data exclude the idea that the inhibitory presynaptic 5-HT receptor on the sympathetic nerves belongs to the 5-HT2 and 5-HT3 receptor class; the pattern of agonist potencies suggests that the receptor is very similar to the 5-HT1D receptor subtype.

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Authors and Affiliations

  1. Institut für Pharmakologie and Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Reuterstrasse 2b, D-5300, Bonn 1, Federal Republic of Germany

    G. J. Molderings, K. Werner & M. Göthert

  2. Klinik für Herz- und Gefüßchirurgie, Rheinische Friedrich-Wilhelms-Universität Bonn, Reuterstrasse 2b, D-5300, Bonn 1, Federal Republic of Germany

    J. Likungu

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  1. G. J. Molderings
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  2. K. Werner
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  3. J. Likungu
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  4. M. Göthert
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Molderings, G.J., Werner, K., Likungu, J. et al. Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT1D subtype. Naunyn-Schmiedeberg's Arch Pharmacol 342, 371–377 (1990). https://doi.org/10.1007/BF00169451

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