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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 343, Issue 4, pp 344–352 | Cite as

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

  • D. I. Wallis
  • L. A. Connell
  • Z. Kvaltinova
Article

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.

Key words

5-Hydroxytryptamine Motoneurones Isolated spinal cord Neonate rat 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • D. I. Wallis
    • 1
  • L. A. Connell
    • 1
  • Z. Kvaltinova
    • 1
  1. 1.Department of PhysiologyUniversity of Wales College of CardiffCardiffUK

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