A pharmacological analysis of the 5-HT receptor mediating inhibition of 5-HT release in the guinea-pig frontal cortex

Middlemiss, Derek N.; Bremer, Margaret E.; Smith, Susan M.

doi:10.1016/0014-2999(88)90476-1

Cited by 81 publications

(17 citation statements)

References 30 publications

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“…The results of this study confirm the weak partial agonist activity of metergoline at the dog saphenous vein 5-HT1-like receptor. It is of interest to note, however, that studies using a different central 5-HTlD receptor model (Middlemiss et al, 1988) found methysergide and metergoline to be weak antagonists or partial agonists. These data are in keeping with those obtained in this study, and support the notion that brain 5-HTID receptors and the dog saphenous vein 5-HT1-like receptor may be similar.…”

Section: Discussionmentioning

confidence: 99%

Studies on the mechanism of 5‐HT₁ receptor‐induced smooth muscle contraction in dog saphenous vein

Sumner

Feniuk

McCormick

et al. 1992

British J Pharmacology

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1 We have investigated the mechanism of smooth muscle contraction evoked by activation of 5-HT1-like receptors in dog isolated saphenous vein. 2 In the presence of the 5-HT2 receptor antagonist, ritanserin (0.1pM), concentration-effect curves (lOnM-300pM) for 5-hydroxytryptamine (5-HT)-induced smooth muscle contraction were biphasic. This could be attributed to a direct action on 5-HT1-like receptors at low concentrations of 5-HT (10nm-1OpM) and an indirect (through the release of noradrenaline from sympathetic neurones) activation of postjunctional a-adrenoceptors at higher 5-HT concentrations. In contrast, concentration-effect curves (100nM-tOOpM) for sumatriptan-induced contractions were not biphasic, and were due solely to activation of 5-HT1-like receptors. 3 Smooth muscle contractions evoked either by low concentrations of 5-HT or by sumatriptan were abolished by removal of extracellular calcium and were markedly inhibited, but not abolished, by the calcium channel blocker, verapamil (1-30pM). In contrast, contractions evoked by high concentrations of 5-HT were markedly less sensitive to removal of extracellular calcium or to verapamil.4 5-HT and sumatriptan also inhibited (to a maximum of about 50%) prostaglandin E2 (PGE2 ,5 pM)-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) formation. This effect was mimicked by the a2-adrenoceptor agonist, azepexole (B-HT933) but not by the a1-adrenoceptor agonist, methoxamine. 5 In contrast to mediation of smooth muscle contraction, the 5-HT1-like receptor-mediated inhibition of PGE2-stimulated cyclic AMP formation evoked by 5-HT or sumatriptan was not attenuated by removal of extracellular calcium or by verapamil (1 PM).6 A directly-acting inhibitor of adenylyl cyclase, 2',3'-dideoxyadenosine (1 mM) inhibited PGE2-stimulated cyclic AMP formation but did not produce smooth muscle contraction. 7 These results suggest that contractile responses of dog isolated saphenous vein arising through activation of 5-HT1-like receptors are associated with both an influx of extracellular calcium ions (to a large extent via voltage-dependent channels) and an inhibition of adenylyl cyclase. However, although these two responses are coupled to the same receptor, they appear to be independent.

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Section: Discussionmentioning

confidence: 99%

Studies on the mechanism of 5‐HT₁ receptor‐induced smooth muscle contraction in dog saphenous vein

Sumner

Feniuk

McCormick

et al. 1992

British J Pharmacology

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“…Furthermore, sumatriptan has little or no affinity for 5-HT 1C or 5-HT 2 receptors and therefore it is unlikely that these receptors are involved in its therapeutic action (1,16). Brain slice transmitter release studies have shown that sumatriptan acts as an agonist at the terminal 5-HT-autoreceptor in the guinea-pig (20). These 5-HT-autoreceptors could possibly be of the 5-HT 1D type, although the significance of their activation in terms of behaviour is unknown.…”

Section: Discussionmentioning

confidence: 99%

Lack of Antinociceptive Activity of Sumatriptan in Rodents

Skingle¹,

Birch²,

Leighton³

et al. 1990

Cephalalgia

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“…A small proportion of 5-HT 1B receptors in the SNr have been assumed to work as 5-HT autoreceptors on 5-HT terminals derived predominantly from the dorsal raphe nucleus (Bruinvels et al, 1992(Bruinvels et al, , 1993Lavoie and Parent, 1990;Steinbü sch, 1981;Streit, 1980;Waeber and Palacios, 1992). On the basis of studies of 5-HT release in the prefrontal cortex and hippocampus, it has been inferred that agonists acting at 5-HT 1B receptors, inhibit Ca 21 -dependent release of 5-HT (Hoyer and Middlemiss, 1989;Limberger et al, 1991;Maura et al, 1986;Middlemiss et al, 1988).…”

Section: Pharmacological Studiesmentioning

confidence: 98%

Real‐time measurement of stimulated 5‐hydroxytryptamine release in rat substantia nigra pars reticulata brain slices

Iravani

Kruk

1997

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Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure 5-HT signals following electrical or chemical stimulation in rat substantia nigra pars reticulata slices. Chemical stimulation with (+)-amphetamine or veratrine gave signals which were indistinguishable from those of exogenous 5-HT. Electrical stimulation of sufficient duration gave voltammetric signals which were characteristic of 5-HT. Release of dopamine was not detected following either chemical or electrical stimulation. The 5-HT signals were attenuated by TTX and enhanced by fluvoxamine. It was not possible to demonstrate regulation of 5-HT release in the SNr by 5-HT1B autoreceptors using CGS 12066A or methiothepin. Signal following electrical stimulation were not enhanced by either benztropine or GBR12909, or modified in the presence of either quinpirole or sulpiride. We conclude that 5-HT release can be detected voltammetrically in the SNr; 5-HT release is likely to be from axon terminals, but somatodendritic DA release could not be detected.

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A pharmacological analysis of the 5-HT receptor mediating inhibition of 5-HT release in the guinea-pig frontal cortex

Cited by 81 publications

References 30 publications

Studies on the mechanism of 5‐HT₁ receptor‐induced smooth muscle contraction in dog saphenous vein

Studies on the mechanism of 5‐HT₁ receptor‐induced smooth muscle contraction in dog saphenous vein

Lack of Antinociceptive Activity of Sumatriptan in Rodents

Real‐time measurement of stimulated 5‐hydroxytryptamine release in rat substantia nigra pars reticulata brain slices

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A pharmacological analysis of the 5-HT receptor mediating inhibition of 5-HT release in the guinea-pig frontal cortex

Cited by 81 publications

References 30 publications

Studies on the mechanism of 5‐HT1 receptor‐induced smooth muscle contraction in dog saphenous vein

Studies on the mechanism of 5‐HT1 receptor‐induced smooth muscle contraction in dog saphenous vein

Lack of Antinociceptive Activity of Sumatriptan in Rodents

Real‐time measurement of stimulated 5‐hydroxytryptamine release in rat substantia nigra pars reticulata brain slices

Contact Info

Product

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Studies on the mechanism of 5‐HT₁ receptor‐induced smooth muscle contraction in dog saphenous vein

Studies on the mechanism of 5‐HT₁ receptor‐induced smooth muscle contraction in dog saphenous vein