Abstract
To understand the action and mechanism of hypotaurine, an immediate precursor of taurine, on orofacial nociceptive processing, we examined the direct effects and receptor types involved in hypotaurine-induced responses using the whole-cell patch clamp technique in the substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) of immature mice. Under the condition of high-chloride pipette solution, hypotaurine elicited inward currents or upward deflections of membrane potential, which increased in a concentration-dependent manner (30–3000 μM) with the EC50 of 663.8 and 337.6 μM, respectively. The responses to 300 µM hypotaurine were reproducible and recovered upon washout. The 300 µM hypotaurine-induced currents were maintained in the presence of TTX, CNQX, and AP5, indicating direct postsynaptic action of hypotaurine on SG neurons. Responses to both low (300 µM) and high (1 or 3 mM) concentrations of hypotaurine were completely and reversibly blocked by the glycine receptor antagonist strychnine (2 µM), but unaffected by the GABAA receptor antagonist gabazine (3 µM) which blocks synaptic GABAA receptors at low concentration. Furthermore, responses to 300 µM hypotaurine and a maximal concentration of glycine (3 mM) were not additive, indicating that hypotaurine and glycine act on the same receptor. Hypotaurine-induced currents were partially antagonized by picrotoxin (50 µM) which blocks homomeric glycine receptors and by bicuculline (10 µM) which is an antagonist of α2 subunit-containing glycine receptors. These results suggest that hypotaurine-induced responses were mediated by glycine receptor activation in the SG neurons and hypotaurine might be used as an effective therapeutics for orofacial pain.
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This research was supported by the Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2015R1D1A3A01018700).
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Oh, S.M., Bhattarai, J.P., Han, S.K. et al. Effects of hypotaurine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice. Amino Acids 48, 2843–2853 (2016). https://doi.org/10.1007/s00726-016-2321-1
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DOI: https://doi.org/10.1007/s00726-016-2321-1