Anxiolytic Action of Taurine via Intranasal Administration in Mice

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

Potentiation of the glycine response by serotonin on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (I(Gly)). Firstly, we examined with a 5-HT₁ receptor agonist (8-OH-DPAT, 5-HT(1/7) agonist, co-applied with SB-269970, 5-HT₇ antagonist) and antagonist (WAY-100635), but 5-HT₁ receptor agonist did not increase IGly and in the presence of 5-HT₁ antagonist, the potentiation of 5-HT on I(Gly) still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT₂ receptor mimicked and inhibited the enhancing effect of 5-HT on I(Gly) in the SG neurons, respectively. We also verified the role of the 5-HT₇ receptor by using a 5-HT₇ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on I(Gly). Our study demonstrated that 5-HT facilitated I(Gly) in the SG neurons of the Vc through the 5-HT₂ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.

Effects of several harmful factors on expression of glycine receptor α1 subunit in neonatal rat myocardial cells / 中国病理生理杂志

AIM:To study the expression of glycine receptorα1 subunit in neonatal rat myocardial cells and to investigate the effect of lipopolysaccharide (LPS), hypoxia/reoxygenation, isoproterenol (ISO) and high concentration of glucose (HG) on the expression of glycine receptorα1 subunit in the neonatal rat myocardial cells.METHODS:Neonatal rat myocardial cells were cultured in vitro.The expression of glycine receptorα1 subunit was detected by Western blotting. The neonatal rat myocardial cells were treated with LPS (20 mg/L), ISO (100 μmol/L) or high concentration of glucose (25 mmol/L) for 24 h, or were exposed to hypoxia for 3 h followed by reoxygenation for 3 h.Subsequently, the cell viabil-ity was measured by CCK-8 assay, and the expression of glycine receptorα1 subunit was determined by Western blotting. RESULTS:The expression of glycine receptor α1 subunit in the neonatal rat myocardial cells was positively detectable by Western blotting.Compared with control group, no significant difference of the cell viability ( P>0.05) in LPS group, ISO group, hypoxia/reoxygenation group and HG group was observed.The expression of glycine receptor α1 subunit was in-creased (P<0.01) in LPS group, ISO group and hypoxia/reoxygenatio group, but decreased (P<0.01) in HG group. CONCLUSION:Glycine receptorα1 subunit exists in the neonatal rat myocardial cells.A certain concentration of LPS or ISO, or hypoxia/reoxygenation for a certain period upregulate the expression of glycine receptorα1 subunit, but HG down-regulates the expression of glycine receptor α1 subunit in cultured neonatal rat myocardial cells.

Glycine- and GABA-mimetic Actions of Shilajit on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice

Shilajit, a medicine herb commonly used in Ayurveda, has been reported to contain at least 85 minerals in ionic form that act on a variety of chemical, biological, and physical stressors. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Shilajit has been reported to be an injury and muscular pain reliever but there have been few functional studies of the effect of Shilajit on the SG neurons of the Vc. Therefore, whole cell and gramicidin-perfotrated patch clamp studies were performed to examine the action mechanism of Shilajit on the SG neurons of Vc from mouse brainstem slices. In the whole cell patch clamp mode, Shilajit induced short-lived and repeatable inward currents under the condition of a high chloride pipette solution on all the SG neurons tested. The Shilajit-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated Na+ channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, and AP5, an NMDA receptor antagonist. The Shilajit-induced responses were partially suppressed by picrotoxin, a GABAA receptor antagonist, and totally blocked in the presence of strychnine, a glycine receptor antagonist, however not affected by mecamylamine hydrochloride (MCH), a nicotinic acetylcholine receptor antagonist. Under the potassium gluconate pipette solution at holding potential 0 mV, Shilajit induced repeatable outward current. These results show that Shilajit has inhibitory effects on the SG neurons of Vc through chloride ion channels by activation of the glycine receptor and GABAA receptor, indicating that Shilajit contains sedating ingredients for the central nervous system. These results also suggest that Shilajit may be a potential target for modulating orofacial pain processing.

Effect of Strychinine, a Glycine Inhibitor, on the Programmed Cell Death of Motoneurons during the Chick Development

In this study, we report that the treatment of strychinine (STR), an inhibitor of glycine receptor, induced premature onset of programmed cell death (PCD) of developing chick motoneurons (MNs). Treatment of STR on E4 chick embryo increased the apoptosis of MN on E5 when MN PCD does not occur normally. On the other hand, treatment of STR from E3 or E5 for 24 hours did not significantly influence the extent of MN PCD, indicating that the STR effect is developmental stage-specific. However, the expression of glycine receptor isoform was low on E3-4, and other glycine receptor antagonists did not exhibit PCD-promoting activity, suggesting that the STR action on PCD is not related to the glycine receptor activation. Identification of the target molecule for STR action may provide novel mechanism how the onset of developmental PCD is regulated.

Immunohistochemical Localization of Glycine Receptor (alpha1+alpha2) in the Auditory Brain Stem of Circling Mouse / 대한해부학회지

Hearing loss in adults can stem from damage to the cochlea and the cochlear nerves inflicted by intense noise, mechanical trauma, or disease. Hearing loss is associated with degenerative changes in central auditory pathways, and hearing deficits are often accompanied by changes in the synaptic organization of the central auditory pathways. In addition to structural rearrangements, hearing loss may induce changes in the strength of synaptic transmissions. These effects may alter both transient and persistent regulation of transmitter release from glutamatergic, glycinergic, and GABAergic pathways in the auditory brain stem. The converging excitatory and inhibitory inputs are exquisitely organized topographically and are aligned perfectly with each other. The LSO and MNTB in the mammalian auditory brain stem provide and receive many glycinergic inputs. Thus, this auditory system is a useful model to study inhibitory synaptic development. However, little is known about the inhibitory synapses in the central nervous system. First, we used immunohistochemistry to compare the glycine receptor (GlyR) distribution in the LSO and MNTB, which project glycinergic inhibitory input into the auditory brainstem, in circling mice (P16), which have a spontaneous mutation in the inner ear, with wild-type mice. The relative immunoreactive density of the LSO was 86.4+/-7.2 in wild-type, 76.7+/-10.7 in heterozygous, and 61.1+/-4.1 in homozygous mice. The relative immunoreactive density of the MNTB was 97.6+/-8.7 in wild-type, 91.7+/-8.9 in heterozygous, and 74.9+/-7.8 in homozygous mice. These results reveal a decreased GlyR immunoreactivity in both the LSO and MNTB, which may be attributable to a postsynaptic decrease in GlyR number. Our model uses congenitally deaf mice, in which both spontaneous and evoked auditory nerve activity are disrupted because of dysfunctional hair cell-spiral ganglion cell transmission. This provides a naturally occurring model that may provide valuable insights into the central aspects of human congenital deafness in addition to the central consequences of a lack of auditory nerve activity. Our results are likely to be relevant to our understanding of the central changes underlying human hereditary deafness.

The glycine receptor / 한양의대학술지

The glycine receptor (GlyR), a member of the pentameric ligand gated ion channel family, is best known for mediating inhibitory neurotransmission in motor and sensory circuits of the spinal cord, and is also present in the brain stem, cerebellum and retina When glycine binds to its site on the external receptor surface, the pore opens allowing Cl- to passively diffuse across the membrane. Because molecules that increase GlyR current may have clinical potentials as muscle relaxant and peripheral analgesic drug, it is important to understand and study the physiology and molecular pharmacology of the GlyR. We review the pharmacology and physiologic properties, structures, function and heritable disorders of glycinergic neurotransmission.

Effects of Nitric Oxide on Inhibitory Receptors of Rod Bipolar Cells of Rat Retina

The effects of nitric oxide (NO) on inhibitory neurotransmitter receptors and some types of inhibitory receptors in dissociated rod bipolar cell (RBC) were investigated. In the whole cell voltage-clamping mode, the gamma-aminobutyric acid (GABA) activated current showed both sustained and transient components. GABA activated transient current was fully blocked by bicuculine, a GABAA receptor antagonist. The cis-4-aminocrotonic acid (CACA), a GABAC receptor agonist, evoked the sustained current that was not blocked by bicuculline (BIC). Glycine activated the transient current. These results indicate that the RBCs possess GABAA, GABAC, and glycine inhibitory receptors. Sodium nitroprusside (SNP), a NO analogue, reduced the currents activated by GABAA receptor only, however, did not reduce the currents activated by either GABAC or glycine receptors. This study signifies further that only NO depresses the fast inhibitory response activated by GABAA receptor in RBC. We, therefore, postulate that NO might depress the light-on/off transient inhibitory responses in RBCs in the rat retina.

Receptor mechanism of general anesthesia / 中国药理学通报

Molecular cloning of cDNAs coding for ligand-gated ion channel subunits makes it possible to study the pharmacology of recombinant receptors with defined subunit compositions. Many laboratories have used these techniques recently to study actions of agents that produce general anesthesia. Most of the volatile and intravenous anesthetics potentiate the function of GABAA receptor to different extent. Glycine, AMPA, kainate,NMDA, and 5-HT3 recepors are also the targets for many anesthetics. Subunit specific actions of some of the agents suggest that construction and testing of certain chimeric receptor subunits may be useful for defining the amino acid sequences responsible for anesthetic actions.

Inhibition of glycine-activated current by total flavones of epimedium in rat spinal dorsal horn neurons / 中国药理学通报

Aim To investigate total flavones of epimedium (TFE) modulation of glycine-activated current (IGly) in acutely dissociated rat spinal dorsal horn neurons. Method Whole-cell patch-clamp technique was used. Result TFE inhibited IGly reversibly in a concentration-dependent manner. It shifted the concentration-response relationship to the right without altering the maximum response and Hill coefficient of the IGly. TFE did not change the ion selectivity of glycine receptor either. Conclusion These results indicate that TFE directly inhibited the glycine receptor response by decreasing the affinity of glycine to its receptor.

Effects of strychnine-sensitive glycine receptor on the hypnotic and analgesic effects of inhalation anesthetics / 中国药理学通报

0.05); in hot-plate test , strychnine at 0.1,0.2,0.4 ?g (it) can significantly and dose dependently decrease the HPPI of the mice treated with aether,enflurane and sevoflurane (P0.05), but at 0.2,0.4 ?g (it) could significantly decrease the HPPI of mice treated with isoflurane(P