title: Effects of hypotaurine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice.
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 EC50of 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 GABAAreceptor antagonist gabazine (3 µM) which blocks synaptic GABAAreceptors 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.
authors: Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 664-14, 1 Ga, Deokjin-Dong, Jeonbuk, Jeonju, 561-756, Republic of Korea.
authors: Sun Mi
authors: SM
authors: Oh
authors: Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 664-14, 1 Ga, Deokjin-Dong, Jeonbuk, Jeonju, 561-756, Republic of Korea.
authors: Janardhan Prasad
authors: JP
authors: Bhattarai
authors: Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 664-14, 1 Ga, Deokjin-Dong, Jeonbuk, Jeonju, 561-756, Republic of Korea.
authors: Seong Kyu
authors: SK
authors: Han
authors: Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 664-14, 1 Ga, Deokjin-Dong, Jeonbuk, Jeonju, 561-756, Republic of Korea. soopark@jbnu.ac.kr.
authors: Soo Joung
authors: SJ
authors: Park
mesh_terms: D000818:Animals; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000008:administration & dosage; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000235:genetics; D013331:Strychnine / Q000008:administration & dosage; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055366:Synaptic Potentials / Q000187:drug effects* / Q000235:genetics; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014278:Trigeminal Nuclei / Q000187:drug effects* / Q000378:metabolism
chemical_list: D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D013654:Taurine; C003949:hypotaurine; C049853:gabazine; D013331:Strychnine
keywords: Glycine receptor; Orofacial nociception; Postsynaptic; Whole-cell patch clamp