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

Abstract

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 greater than or equal to 5-HT greater than 5-carboxamidotryptamine = 5-methoxytryptamine = sumatriptan greater than tryptamine greater than 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.

Characterization of prejunctional 5‐HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat

“…Obviously, the identification of the specific subtype of 5-HTI-like receptor involved in the inhibition by 5-HT in this study will require, as previously discussed, further experiments with selective agonists and antagonists of the various 5-HT, receptor subclasses (Hoyer et al, 1994). In contrast to the results of the present study, both methiothepin and metergoline have proven adequate antagonists if the inhibition to 5-HT is measured as a response unrelated to stimulation of al-adrenoceptors, for example, the inhibition of electrically-evoked release of [3H]-noradrenaline Molderings et al, 1990) or the vasodilatation of the canine external carotid bed resulting from inhibition of the sympathetic discharge .…”

Serotonin and Blood Pressure Regulation

“…Although autoinhibition of serotonergic nerves through 5-HT receptors makes intuitive sense, the finding of 5-HT receptors on adrenergic nerves is less intuitive. The 5-HT 1B/1D receptor class has been found on sympathetic nerve terminals (Feniuk et al, 1979;Shepherd and Vanhoutte, 1985;Göthert et al, 1986Göthert et al, , 1991Molderings et al, 1990). Activation of these receptors results in a reduced NE release from the terminal such that the overall effect is reduced contractile tone.…”

5-HT Receptor Regulation of Neurotransmitter Release

“…In particular, inhibitory presynaptic 5-HT 1B/1D receptors have been identified on the noradrenergic axon terminals of the cardiovascular system of various species both in vitro and in vivo (Charlton et al, 1986;Göthert et al, 1986;Molderings et al, 1987Molderings et al, , 1990Molderings et al, , 1996Medhurst et al, 1997;Morá n et al, 1998;Harris et al, 2002). Therefore, one could expect that the noradrenergic nerve terminals in the CNS might also be endowed with inhibitory presynaptic 5-HT 1B/1D receptors.…”