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      • Effects of hypotaurine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice

        Oh, S. M.,Bhattarai, J. P.,Han, S. K.,Park, S. J. Springer Science + Business Media 2016 Amino acids Vol.48 No.12

        <P>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 mu M) with the EC50 of 663.8 and 337.6 mu M, respectively. The responses to 300 A mu M hypotaurine were reproducible and recovered upon washout. The 300 A mu M 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 A mu M) and high (1 or 3 mM) concentrations of hypotaurine were completely and reversibly blocked by the glycine receptor antagonist strychnine (2 A mu M), but unaffected by the GABA(A) receptor antagonist gabazine (3 A mu M) which blocks synaptic GABA(A) receptors at low concentration. Furthermore, responses to 300 A mu M 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 A mu M) which blocks homomeric glycine receptors and by bicuculline (10 A mu M) which is an antagonist of alpha 2 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.</P>

      • Gonadotrophin-Releasing Hormone (GnRH) Exerts Stimulatory Effects on GnRH Neurones in Intact Adult Male and Female Mice

        Han, S.-K.,Lee, K.,Bhattarai, J. P.,Herbison, A. E. Blackwell Publishing Ltd 2010 Journal of neuroendocrinology Vol.22 No.3

        <P>There is substantial evidence for a role of the neuropeptide gonadotrophin-releasing hormone (GnRH) in the regulation of GnRH neurone secretion but how this is achieved is not understood. We examined here the effects of GnRH on the electrical excitability and intracellular calcium concentration ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) of GnRH neurones in intact adult male and female mice. Perforated-patch electrophysiological recordings from GnRH-green fluorescent protein-tagged GnRH neurones revealed that 3 n<SMALL>M</SMALL>–3 &mgr;<SMALL>M</SMALL> GnRH evoked gradual approximately 3 mV depolarisations in membrane potential from up to 50% of GnRH neurones in male and female mice. The depolarising effect of GnRH was observed on approximately 50% of GnRH neurones throughout the oestrous cycle. However, at pro-oestrus alone, GnRH was also found to transiently hyperpolarise approximately 30% of GnRH neurones. Both hyperpolarising and depolarising responses were maintained in the presence of tetrodotoxin. Calcium imaging studies undertaken in transgenic GnRH-pericam mice showed that GnRH suppressed [Ca<SUP>2+</SUP>]<SUB>i</SUB> in approximately 50% of GnRH neurones in dioestrous and oestrous mice. At pro-oestrus, 25% of GnRH neurones exhibited a suppressive [Ca<SUP>2+</SUP>]<SUB>i</SUB> response to GnRH, whereas 17% were stimulated. These results demonstrate that n<SMALL>M</SMALL> to &mgr;<SMALL>M</SMALL> concentrations of GnRH exert depolarising actions on approximately 50% of GnRH neurones in males and females throughout the oestrous cycle. This is associated with a reduction in [Ca<SUP>2+</SUP>]<SUB>i</SUB>. At pro-oestrus, however, a further population of GnRH neurones exhibit a hyperpolarising response to GnRH. Taken together, these studies indicate that GnRH acts predominantly as a neuromodulator at the level of the GnRH cell bodies to exert a predominant excitatory influence upon GnRH neurones in intact adult male and female mice.</P>

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