Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.
1. To evaluate the implication of taurine in the physiology of supraoptic neurones, we (i) investigated the agonist properties of taurine on glycine and GABAA receptors of supraoptic magnocellular neurones acutely dissociated from adult rats, using whole-cell voltage clamp, (ii) studied the effects of taurine and strychnine in vivo by extracellular recordings of supraoptic vasopressin neurones in anaesthetized rats, and (iii) measured the osmolarity-dependent release of endogenous taurine from isolated supraoptic nuclei by HPLC. 2. GABA, glycine and taurine evoked rapidly activating currents that all reversed close to the equilibrium potential for Cl-, indicating activation of Cl(-)-selective channels. Glycine-activated currents were reversibly blocked by strychnine (IC50 of 35 nM with 100 microM glycine), but were unaffected by the GABAA antagonist gabazine (1-3 microM). GABA-activated currents were reversibly antagonized by 3 microM gabazine, but not by strychnine (up to 1 microM). 3. Responses to 1 mM taurine were blocked by strychnine but not by gabazine and showed no additivity with glycine-induced currents, indicating selective activation of glycine receptors. Responses to 10 mM taurine were partially antagonized by gabazine, the residual current being blocked by strychnine. Thus, taurine is also a weak agonist of GABAA receptors. 4. In the presence of gabazine, taurine activated glycine receptors with an EC50 of 406 microM. Taurine activated at most 70% of maximal glycine currents, suggesting that it is a partial agonist of glycine receptors. 5. In vivo, locally applied strychnine (300 nM) increased and taurine (1 mM) decreased the basal electrical activity of vasopressin neurones in normally hydrated rats. The effect of strychnine was markedly more pronounced in water-loaded rats. 6. Taurine, which is concentrated in supraoptic glial cells, could be released from isolated supraoptic nuclei upon hyposmotic stimulation. Decreases in osmolarity of 15 and 30% specifically enhanced basal release of taurine by 42 and 124%, respectively. 7. We conclude that supraoptic neurones express high amounts of glycine receptors, of which taurine may be regarded as a major natural agonist. We postulate that taurine, which can be released in hyposmotic situations, acts on glycine receptors to exert an inhibitory control on magnocellular neurones during alterations of body fluid homeostasis, implicating an active participation of glial cells in this neuroendocrine regulatory loop.
Hussy
N
N
CNRS-UPR 9055, Montpellier, France. hussy@bacchus.montp.inserm.fr
Deleuze
C
C
Pantaloni
A
A
Desarménien
M G
MG
Moos
F
F
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D004594:Electrophysiology; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006982:Hypertonic Solutions; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009997:Osmotic Pressure; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists*; D013331:Strychnine / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology* / Q000502:physiology; D013654:Taurine / Q000378:metabolism / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D018684:Glycine Agents; D006982:Hypertonic Solutions; D018009:Receptors, Glycine; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; D005998:Glycine