Presynaptic Inhibitory Action of 5‐hydroxytryptamine in Dog Isolated Saphenous Vein

Abstract

The effect of 5‐hydroxytryptamine on contractile responses to sympathetic nerve stimulation has been studied in the dog isolated saphenous vein. Electrical stimulation (0.1 to 10 Hz) of dog saphenous vein strips produced frequency‐dependent contractions. Contractions produced by stimulation at 2 Hz were almost completely blocked by tetrodotoxin (3.1 × 10−8 mol/l) or phentolamine (5.0 × 10−6 mol/l) but mecamylamine (5.0 × 10−6 mol/l) had little effect. This suggests that the contractions were mediated predominantly through noradrenaline release from postganglionic noradrenergic nerves. Contractions produced by intermittent electrical stimulation at 2 Hz were inhibited by 5‐hydroxytryptamine (1.0 × 10−9 to 1.0 × 10−7 mol/l) in a concentration‐dependent manner whilst contractions induced by exogenous noradrenaline were not affected. The inhibitory action of 5‐hydroxytryptamine was most marked at low frequencies of stimulation and with low pulse numbers. High external calcium concentrations (3.9 and 5.2 × 10−3 mol/l) reduced the inhibitory action of 5‐hydroxytryptamine. Cyproheptadine (1.0 × 10−8 mol/l to 1.0 × 10−6 mol/l) or morphine (1.0 × 10−7 mol/l to 1.0 × 10−5 mol/l) did not antagonize the inhibitory action of 5‐hydroxytryptamine. Methysergide (1.0 × 10−7 mol/l) slightly reduced the contractions produced by electrical stimulation and only weakly antagonized the action of 5‐hydroxytryptamine. It is suggested that a 5‐hydroxytryptamine receptor exists presynaptically in the dog isolated saphenous vein strip and that stimulation of this receptor by low concentrations of 5‐hydroxytryptamine inhibits the release of noradrenaline from noradrenergic nerves. This receptor type is resistant to blockade by ‘classical’ 5‐hydroxytryptamine antagonists.

Further characterization of the 5‐HT receptor mediating vascular relaxation and elevation of cyclic AMP in porcine isolated vena cava

“…In addition to these receptors mediating smooth muscle relaxation, a 5-HT1-like receptor which mediates smooth muscle contraction and inhibition of neuronal transmitter release has been described, and this receptor is selectively activated by the novel agonist GR43175 (Feniuk et al, 1979;1985;Humphrey et al, 1988). Hence, the lack of effect of GR43175 in the porcine vena cava (as an agonist or antagonist) provides further evidence for the proposed sub-division of 5-HT1-like receptors .…”

Lack of effect of sumatriptan and UK‐14,304 on capsaicin‐induced relaxation of guinea‐pig isolated basilar artery

“…In the present study, however, neither sumatriptan nor UK-14,304, at concentrations which should maximally activate presynaptic 5-HT, receptors (Humphrey et al, 1988) or C2-adrenoceptors (Cambridge, 1981), modified capsaicin-induced relaxations in the GPBA in vitro. Lowering extracellular calcium, a method which can be used to enhance detection of presynaptic mechanisms (Feniuk et al, 1979) failed to unmask any inhibitory effect of sumatriptan.…”

Differential classification of vascular smooth muscle and endothelial cell 5‐HT receptors by use of tryptamine analogues

“…Yet a further 5-HT receptor, which is clearly not of the 5-HT2 type (Feniuk et al, 1985), has been shown to mediate contraction of certain cutaneous and cerebral blood vessels (Apperley et al, 1980;Mfiller-Schweinitzer, 1981;Bradley et al, 1986a) and to inhibit release of noradrenaline from sympathetic nerve terminals (Feniuk et al, 1979;Engel et al, 1983;Cohen, 1985). This receptor shares in common with the endothelial and smooth muscle relaxant 5-HT receptors a susceptibility to blockade by low concentrations ofmethiothepin (Apperley & Humphrey, 1986) and a resistance to blockade by ketanserin (Cohen, 1985;Bradley et al, 1986a;Feniuk et al, 1985).…”