An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney

1 It has recently been shown that the increase in external carotid blood flow induced by 5-hydroxytryptamine (5-HT) in the anaesthetized dog, being mimicked by 5-carboxamidotryptamine dose-dependent increases in external carotid blood flow (without changes in mean arterial blood pressure or heart rate) with the following rank order of agonist potency: 5-CT>>5-HT> 5-methoxytryptamine > sumatriptan. Interestingly, sumatriptan-induced vasodilatation was followed by a more pronounced vasoconstriction. 3 The external carotid vasodilator effects of 5-HT, 5-CT, 5-methoxytryptamine and sumatriptan were dose-dependently and specifically antagonized by metergoline (10, 30 and/or 100figkg -, i.v.). In addition, 5-methoxytryptamine-and sumatriptan-induced vasodilator effects were, respectively, markedly inhibited or abolished after vagosympathectomy, as previously shown for 5-CT and 5-HT. 4 Sumatriptan showed tachyphylaxis in its vasodilator component and antagonized 5-HT-induced external carotid vasodilatation in a specific manner, suggesting that a common site of action may be involved. 5 Taken together, the above results support our contention that 5-HT, 5-CT, 5-methoxytryptamine and sumatriptan produce external carotid vasodilatation in the dog by an action that might primarily involve a prejunctional inhibition on carotid sympathetic nerves; a secondary component of this vasodilator response may be postsynaptic (endothelium-dependent and/or even directly on the vasculature). Based on the rank order of agonist potency, inhibition by vagosympathectomy and blockade by metergoline, we suggest that the inhibitory prejunctional 5-HT,-like receptors mediating external carotid vasodilatation in the dog closely resemble the 5-HTD receptor subtype. The pharmacological profile of these receptors is similar (sympathetic nerves of the rat kidney and human saphenous vein, as well as porcine coronary endothelium) to other putative 5-HTID receptors mediating vascular responses.

Section: Systemic and Carotid Haemodynamic Changesmentioning

confidence: 68%

Section: Systemic Haemodynamic Variablesmentioning

confidence: 99%

Section: Systemic and Carotid Haemodynamic Changesmentioning

confidence: 99%

See 1 more Smart Citation

The 5‐HT₁‐like receptor mediating the increase in canine external carotid blood flow: close resemblance to the 5‐HT_1D subtype

Villalón

Terrón

1994

“…Although (-)-pindolol does not antagonize all of the effects considered to be mediated by 5-HT1-like receptors (Feniuk et al, 1983;Charlton et al, 1986), it does bind with high affinity to the putative 5-HTlA-and 5-HTlB-receptors and antagonizes functional responses thought to be mediated at these receptors (Middlemiss, 1984;Engel et al, 1986;Tricklebank et al, 1985;. Also, of greater relevance to the present study, Kennett et al (1987) have shown that (-)-pindolol and (±)-cyanopindolol antagonized the anorectic effects of the putative 5-HT1B-receptor agonist, RU24969.…”

Section: Discussionmentioning

confidence: 95%

Quipazine reduces food intake in the rat by activation of 5‐HT₂‐receptors

Hewson

Leighton

Hill

et al. 1988

1 To determine which subtype(s) of 5-hydroxytryptamine (5-HT) receptor are involved in the anorectic action of quipazine, the ability of selective antagonists at 5-HT2-and 5-HT3-receptors, and an antagonist at 5-HT1-like receptors, to block this response were investigated in non-deprived rats, trained to eat a palatable diet. 2 Quipazine (0.5-8mg kg-, i.p.) produced a dose-related reduction in the intake of palatable diet. 3 The anorectic effect of 4 mg kg1 quipazine was antagonized by the nonselective 5-HT-receptor antagonist methysergide (5 mg kg 1, i.p.) and by the selective 5-HT2-receptor antagonists ketanserin (1mgkg-1 and 2.5mgkg-1, i.p.) and ritanserin (0.5mgkg-1 and lmgkg-1, i.p.). The selective 5-HT3-receptor antagonist GR38032F (1mgkg-1, i.p.) and (-)-pindolol (4mgkg-, i.p.), which blocks some of the effects mediated at 5-HT1-like receptors, did not block the reduction in food intake produced by this dose of quipazine. 4 None of the 5-HT-receptor antagonists had any effect on food intake when they were administered alone, suggesting that endogenous 5-HT is not involved in the tonic control of food intake under the conditions of these experiments. 5 It is concluded that the anorectic action of quipazine is mediated, at least in part, by activation of 5-HT2-receptors.

“…With respect to the latter, several lines of pharmacological evidence have shown that 5-HT inhibits the contractile responses to adrenergic nerve stimulation in blood vessels by activation of prejunctional 5-HTl-like receptors; these blood vessels include, amongst others, the canine (Humphrey et al, 1988) and human ) saphenous veins; the canine common carotid (Mylecharane & Phillips, 1989), external carotid Villalon et al, 1993) and femoral (Feniuk et al, 1981) arterial beds; the rat kidney (Charlton et al, 1986) and vena cava (Molderings et al, 1987); and the porcine coronary artery (Molderings et al, 1989). 'Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

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

Villalón

Contreras

Juan³

et al. 1995

1 It has recently been shown that continuous infusions of 5-hydroxytryptamine (5-HT) are able to inhibit, in a dose-dependent manner, the pressor responses induced by preganglionic (T7-Tg) sympathetic stimulation in pithed rats pretreated with desipramine (50 mg kg- ', i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03-1 Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5-HT (up to 5.6 pg kg-' min-'). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-HT. 2 The inhibition induced by 5.6 Mg kg-' min-' of 5-HT on sympathetically-induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg-'), ritanserin (0.1 mg kg-'), MDL 72222 (0.15 mg kg-') or tropisetron (3 mg kg-'), which did not modify the sympatheticallyinduced pressor responses per se, but was significantly antagonized by the 5-HTI-like and 5-HT2 receptor antagonist, methysergide (0.3 mg kg-1), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se. 3 Unexpectedly and contrasting with methysergide, the 5-HT,-like and 5-HT2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg-') and metergoline (1 and 3 mg kg-'), apparently failed to block the above 5-HT-induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically-induced pressor responses per se, presumably by blockade of vascular a,-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HTI-like receptors. 4 Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HTI-like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5-HT with the following rank order of agonist potency: 5CT > > 5-HT > metergoline > methysergide. 5 Taken together, the above results suggest that the inhibitory action of 5-HT on the electricallyinduced pressor responses is primarily mediated by an action on inhibitory prejunctional 5-HTI-like receptors leading to a decrease in the sympathetic nerve discharge. Interestingly, 5-HT-induced excitatory mechanisms could be made manifest once the inhibitory action of 5-HT had been antagonized.