Activation of CD8+T cells regulated by γ-aminobutyric acid and its receptors / 器官移植

Objective To evaluate the effect of γ-aminobutyric acid (GABA) and its receptors upon the proliferation of CD8+T cells.Methods The splenic CD8+T cells of Balb/c mice were obtained by CD8+f cell magnetic bead sorting kit.Under the effect of CD3/CD28-activated magnetic bead,CD8+T cells were stimulated by different concentrations of GABA.5-bromo-2-deoxyuridine (BrdU) labeling and flow cytometry were performed to detect the proliferation of CD8+T cells.The expression levels of GABA-A and GABA-B receptor before and after CD8+T cell activation were compared by fluorescent quantitative real-time polymerase chain reaction (PCR).Result Flow cytometry result revealed that GABA could inhibit the proliferation of activated CD8+T cells,manifested as significant decrease in the quantity of CD152+CD8+T cells.Fluorescent quantitative real-time PCR demonstrated that GABA-A receptor subtypes α2,α6 and GABA-B receptor subtype 1a were expressed only when the CD8+T cells were activated.After CD8+T cell activation,the quantity of GABA-A receptor subtypes α3,αs,β2,β3,γ1,γ2 and θ were significantly increased,whereas the quantity of GABA-B2R and GABA-B1b did not significantly differ before and after CD8+T cell activation.Conclusions GABA can suppress the proliferation of activated CD8+T cells.The activation of CD8+T cells is regulated by GABA receptors.However,the underlying mechanism remains to be elucidated.

Participação de receptores GABA B na modulação do consumo etílico em ratos Wistar / Involvement of GABA B receptor on ethylic consumption modulation in Wistar rats

Introdução: o baclofeno, uma droga agonista seletivo de GABA B, tem sido apontado como uma nova opção de tratamento do etilismo. Neste estudo avaliou-se o efeito do baclofeno no consumo etílico em ratos Wistar. Materiais e Métodos: o experimento ocorreu em quatro fases: exposição, abstinência, reexposição e tratamento. Os animais foram alocados em grupos: 1, 2, 3 e 4 (n=5 por grupo), expostos à água pura, solução hidroalcoólica (SHA) 5% e SHA 10%; grupo 5 (subdividido em A, B e C N =5 por subgrupo) e grupo 6 (n=5), ambos expostos a apenas água pura. A administração de baclofeno via intraperitoneal destinou aos grupos 1, 2, 3 e 5 em diferentes doses. Nos demais grupos, administrou-se placebo. Aferiu-se o consumo das soluções em todas as fases, para fins comparativos. Resultados: o baclofeno, na dose de 1mg/Kg, reduziu o consumo de SHA 10% no grupo 1, que apresentou maior consumo etílico durante o experimento. Os demais grupos apresentaram menor consumo das SHA ofertadas, sem redução da ingesta etílica após administração da droga nas doses de 2 e 3mg/Kg. Conclusão: baclofeno reduziu etilismo apenas em animais com maior consumo etílico prévio à sua administração. O peso dos animais não foi fator determinante na resposta à droga. A dose efetiva no tratamento dos efeitos da privação alcoólica foi a de menor concentração (1mg/kg).

Introduction: Baclofen, a GABA B agonist, has been pointed as a new drug on the alcohol consumption treatment. This study has evaluated baclofen ́s effect on ethanol consumption in Wistar rats. Materials and Methods: four phases protocol: exposure, abstinence, re-exposure and treatment. Animals were allocated into groups: 1, 2, 3 and 4 (n=5 per group), exposed to pure water, 5% ethanol solution and 10% ethanol solution. Group 5 (subdivided into A, B and C, n=5 by subgroup) and group 6 (n=5), exposed to pure water. Baclofen intraperitoneal administration was destined to groups 1, 2, 3 and 5 (A, B and C) in different doses. The remaining groups received saline solution as control. Solutions consumption was assessed in all phases for comparative purposes. Results: Baclofen at 1mg/Kg reduced the 10% (vv) water-alcohol consumption in animals from Group 1, which also presented greater ethanol consumption during the experiment. The other groups showed a lower water - alcohol consumption and did not show an ethanol intake reduction after the drug administration in both 2 and 3mg/Kg doses. Conclusion: Baclofen only reduces alcoholism in animals with higher ethanol consumption. Animals weight is not a determining factor in ethanol consumption or in baclofen response. The effective baclofen dose in treating the deprivation alcohol effects was observed in the lowest concentration, corresponding to 1mg/Kg dose.

Change of GABA_B Receptor in Medulla of Trigeminal Neuralgia on Rats / 上海第二医科大学学报

Objective To assess the relationship between GABA_(B) receptor in medulla and trigeminal neuralgia on rats. Methods Twelve SD rats were randomly divided into 4 groups,3 for each group.Group A and B were surgical groups,while Group C and D were sham surgical ones.In the surgical group,right unilateral chronical constriction injury(CCI) of rats was produced by placing loose chromic gut ligature around the infraorbital nerve(ION).In the sham surgical group,the ION was only exposed using the same procedure but not ligated.Mechanical response threshold was observed before operation and 3,6,9,12 and 15 days after operation.Medullas of rats in group A and B were taken to measure the quantity of GABA_(B) receptor by real-time PCR 9 days after operation,and medullas of rats in group C and D were done 15 days after operation. Results Compared with the sham surgical group,an allodynia to mechanical stimulation on the territory of ligated ION was found from the ninth to fifteenth day after operation in surgical group(P

IMMUNOCYTOCHEMICAL LOCALIZATION OF GABA-A-AND GABA-B-RECEPTOR IN THE MESENCEPHALIC TRIGEMINAL NUCLEUS OF THE RAT / 解剖学报

Objective The immunocytochemical localizations of GABA\-A\| and GABA\-B\|receptor in the mesencephalic trigeminal nucleus(Vme) of the rat were examined in order to provide morphological evidence for a possible functional analysis of GABA\|receptor in the transmission and modulation of the orofacial region trigeminal proprioceptive sensory information. Methods An immunocytochemical staining method was used in the present study,and immunostained sections were observed under light microscope. Results Many neuronal cell bodies,fibers and terminals with dense GABA\-A\| and GABA\-B\|receptor\|like immunoreactivity(\|LI) were observed to be localized in Vme,and different subunits of GABA\|receptor\|LI showed the morphological difference in their distribution:1.Immunoreactivity for GABA\-B R1 subunit was intensely distributed in the cell bodies of Vme neurons,whereas the weak immunoreactivity for GABA\-BR2 subunit was only observed in the region surrounding the somata of Vme neurons which showed negative GABA\-BR2\|LI;2.A considerable number of GABA\-A\|like immunoreactive neurons,fibers and terminals were also found in Vme.It was involved four kinds of subunits(?1,?2,?3 and ?).The heavy immunoreactivity for GABA\-AR?1 and GABA\-AR?3 subunits were only seen in the cell bodies of Vme neurons.On the other hand,the immunoreactivity for GABA\-AR?2 and GABA\-AR? subunits was only observed in the fibers and terminals in the region surrounding the somata of Vme neurons,which showed negative immunoreactivity for above subunits;3.Dense GABA\-BR2\|,GABA\-AR?2\| and GABA\-AR?\|LI fibers and terminals surround the somata of Vme neurons,especially for GABA\-AR?2\|LI.Conclusion\ The present results suggest that there are some differences in the distribution of the various subunits of GABA\-A\| and GABA\-B\|receptor in Vme.It is likely that the inhibitory regulation and control effects of GABAergic terminals on the transmission of orofacial region proprioceptive sensory information might be mainly mediated through GABA\-AR?1 and GABA\-AR?3 subunits in somata of Vme neurons.