A novel 5-HT receptor or a combination of 5-HT receptor subtypes may mediate depression of a spinal monosynaptic reflex in vitro

Crick, H.; Manuel, N.A.; Wallis, David

doi:10.1016/0028-3908(94)90188-0

Cited by 19 publications

(24 citation statements)

References 14 publications

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“…The blockade of this action by spiperone is usually interpreted (see Wu et al, 1991;Crick et al, 1994) as interaction with 5-HTlA receptors. However, as can been seen from Figure 4, this interpretation may be incorrect, since R (+ )-8-OH-DPAT depression of the MSR was unaffected by the selective 5-HTlA antagonist, spiroxatrine (0.1 gM), but very effectively antagonized by ketanserin (0.1 Mm).…”

Section: Agonist Actions Of Sumatriptan and Gr 85548mentioning

confidence: 99%

“…chemical treatment, depresses the MSR via receptors blocked by 5-HT2 receptor antagonists, such as ketanserin and ritanserin, and also by spiperone and methiothepin (Wallis et al, 1993a,b). Crick et al (1994) proposed that an avid uptake mechanism for 5-HT effectively protects synaptic 5-HT receptors from exogenous 5-HT but does not prevent released 5-HT, which presumably transiently reaches much higher concentrations, from activating ketanserin-sensitive receptors. At higher concentrations, 5-HT directly depolarizes spinal motoneurones (EC" 1.4 yM in the presence of citalopram, Elliott & Wallis, 1992) via an action at 5-HT2 receptors (Wang & Dun, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…Further, the finding that depression of the MSR by certain 5-HT agonists could be blocked by 5-HT antagonists, whereas the action of 5-HT could not (Crick et al, 1994), suggested that 5-HTIA, 5-HTIB or 5-HT2 receptors, or 2 or more of these, Bridsh Joumal of PhamacolM (1995PhamacolM ( ) 116, 2647PhamacolM ( -2654 N.A. Manuel et at 5-HT agonist actions blocked by ketanwln might mediate reflex depression.…”

Section: Introductionmentioning

confidence: 99%

“…Manuel et at 5-HT agonist actions blocked by ketanwln might mediate reflex depression. 5-HT applied to the cord acts through a receptor incapable of being blocked by a combination of 5-HT1, 5-HT2 and 5-HT3 antagonists, and probably does not involve 5-HT4 receptors (Crick et al, 1994). The discovery that ketanserin was able to block the actions of sumatriptan on the reflex hinted at a novel mode of 5-HT receptor-mediated synaptic depression in the rat.…”

Section: Introductionmentioning

confidence: 99%

“…The discovery that ketanserin was able to block the actions of sumatriptan on the reflex hinted at a novel mode of 5-HT receptor-mediated synaptic depression in the rat. Sumatriptan is one of a number of selective 5-HT receptor agonists which have a potent depressant action on the MSR (Hendrikse et al, 1992;Crick et al, 1994). We describe here recent experiments with sumatriptan, the related ligand N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane sulphonamide (GR 85548) and 5-carboxamidotryptamine (5-CT) which attempt to examine whether 5-HTlD rather than 5-HTIB receptors might be responsible for some of the reported actions of 5-HT receptor agonists.…”

Section: Introductionmentioning

confidence: 99%

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Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

Manuel¹,

Wallis²,

Crick³

1995

British J Pharmacology

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1 The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and R( + )-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and also by the selective 5-HTlD agonists, sumatriptan and N-methyl-3-(1-methyl-1-piperidinyl)-1H-indole-5-ethane sulphonamide (GR 85548).2 Ketanserin (1 gM) and methiothepin (1 gM) reduced the duration of depressions elicited by 5-CT, but not those produced by 5-HT, sumatriptan, GR 85548, methysergide or 8-OH-DPAT.3 The IC50 for MSR depression by 5-CT was 3.6, 2.1 -6.2nM (n=4), by sumatriptan was 15.2, 12.9-18.0nM (n=32), by GR 85548 was 18.4, 11.7-29.1 nM (n =12), by methysergide was 29.8, 10.2-87.1nM (n=4) and by 8-OH-DPAT was 0.21, 0.11-0.43 MM (n=3) (geometric means and 95% confidence limits). 4 Ketanserin (0.1 or 1 UM) antagonized competitively responses to sumatriptan (apparent pA2 7.8 ± 0.1, n = 5), GR 85548 (apparent pA2 7.6, unpaired data, n = 5), methysergide (apparent pA2 7.9 ± 0.12, n=4) and 8-OH-DPAT (apparent pA2 8.3 ± 0.1, n= 3). Concentration-response curves to 5-CT showed a smaller, parallel shift to the right (apparent pA2 6.8 ± 0.1, n = 4), but responses to 5-HT were unaffected by ketanserin (1 gM) (n = 4). Neither with these concentrations nor with concentrations in the range 1-3 nm was there any unequivocal blockade of responses to sumatriptan. 9 It is concluded that sumatriptan, GR 85548, methysergide and 8-OH-DPAT depress the MSR in the neonate rat spinal cord via ketanserin-sensitive receptors, which have some similarities to 5-HTLIT1 receptors but which are not blocked by GR 127935. 5-HT released by tryptaminergic pathways may act via the same receptors to depress the MSR. 5-HT applied to the cord probably acts via a different, possibly novel 5-HT receptor to depress the MSR.

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Section: Agonist Actions Of Sumatriptan and Gr 85548mentioning

confidence: 99%