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Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord

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Summary

Using the hemisected spinal cord of the neonate rat, the effects of altered external Ca, thyrotrophin-releasing hormone (TRH) and a number of antagonists were tested on depolarizations evoked by 5-hydroxytryptamine (5-HT). Responses of populations of motoneurones were recorded via a ventral root. 5-Hydroxytryptamine depolarizations were not Ca-dependent but were enhanced in amplitude in Ca-free solutions. Raised Mg reversed this enhancement. 5-Hydroxytryptamine depolarizations persisted in the presence of Mn (1.53 mmol/l). TRH depolarized motoneurones; there was no evidence of modulation of 5-HT responses on concurrent application of TRH. Ritanserin (0.1 μmol/l) had a modest blocking action on 5-hydroxytryptamine depolarizations reducing the maximum; 1μmol/l ritanserin caused a greater antagonism which was unsurmountable (pIC50 5.2). Ritanserin (0.1 or 1 μmol/l) did not depress responses to noradrenaline (NA). Ketanserin (0.1 μmol/l) caused a blockade of slow onset, equilibrium with the receptors requiring 1 h. Blockade by 0.01, 0.1 and 1 μmol/l ketanserin was concentration-dependent (pIC50 6.2). Ketanserin 1 μmol/l, but not at lower concentrations, depressed noradrenaline responses. Mianserin (0.1 μmol/l) also caused a blockade of slow onset; 0.1 or 1 μmol/l produced a flattening of the 5-hydroxytryptamine concentration-response curve but did not depress noradrenaline responses (pIC50 4.7). The pIC50 for spiperone was 8.0. DOI (10–100 μmol/l) had no detectable agonist action but at concentrations of 0.01 and 0.1 μmol/l it acted as an antagonist. Equilibration with the receptors occurred over 2 h. DOI (0.01 μmol/l) depressed 5-hydroxytryptamine but not noradrenaline responses; higher concentrations of DOI also depressed noradrenaline responses. The pharmacological profile of the 5-hydroxytryptamine receptor mediating depolarization of spinal and facial motoneurones suggests that it belongs to the 5-HT1C-5-HT2, group of 5-hydroxytryptamine receptors but is not identical to 5-HT1C or the 5-HT2 CNS binding sites. Alternatively, the response might arise from a mixed population of 5-HT1-like and 5-HT2 receptors.

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Author notes

  1. Z. Kvaltinova

    Present address: Centre of Physiological Sciences, Slovak Academy of Sciences, Institute of Experimental Pharmacology, Dubravska cesta 9, Bratislava, Slovakia

Authors and Affiliations

  1. Department of Physiology, University of Wales College of Cardiff, PO Box 902, CF1 1SS, Cardiff, UK

    D. I. Wallis, L. A. Connell & Z. Kvaltinova

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  1. D. I. Wallis
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  2. L. A. Connell
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  3. Z. Kvaltinova
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Wallis, D.I., Connell, L.A. & Kvaltinova, Z. Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord. Naunyn-Schmiedeberg's Arch Pharmacol 343, 344–352 (1991). https://doi.org/10.1007/BF00179038

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