Potentiation of chloride responses to glycine by three 5-HT3 antagonists in rat spinal neurones.
1. Modulations of Cl- responses to glycine by 5-hydroxytryptamine ligands were studied in cultured spinal neurones, by the whole-cell recording technique. 2. Three 5-HT3 antagonists were found to potentiate reversibly responses to low concentrations of glycine. Potentiations were induced by micromolar concentrations of LY-278,584 (1-10 microM) and by concentrations of MDL-72222 or ICS-205,930 between 10 nM and 1 microM. 3. Potentiations were observed over the whole voltage range without any change in the reversal potential of the glycine responses and without affecting the resting conductance. 4. The degree of potentiation was variable among cells. It increased with the concentration of the modulator, but only up to 100 nM for MDL-72222 and ICS-205,930. 5. The potentiation appeared to result from an increase in the affinity for glycine of glycine receptors. 6. Neither the blockade of glycine uptake by Na+ removal, nor the excision of membrane patches prevented the potentiation. 7. At high concentrations (10 microM), both MDL-72222 and ICS-205,930 had, in contrast, a blocking effect on glycine responses. 8. Potentiation by LY-278,584 and a dose-dependent modulation by MDL-72222 were also observed for taurine responses. 9. The effects on glycine responses of various ligands of 5-HT3 receptors (including agonists) are discussed. The ability of LY-278,584, MDL-72222 and ICS-205,930 to potentiate glycine responses appears to be independent of their known 5-HT3 receptor antagonist properties. It would be interesting to look for chemically related drugs that would be specific potentiators of glycine responses.
Chesnoy-Marchais
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Laboratoire de Neurobiologie, Ecole Normale Superieure, Paris, France.
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects*
D002712:Chlorides; D012702:Serotonin Antagonists; D005998:Glycine