Role of GABAAα3 and GABAB receptors in ventrolateral periaqueductal gray in rats with acute pain / 临床麻醉学杂志

Objective To investigate the role of GABAAα3and GABAB receptors in the ventrolateral periaqueductal gray in the development of paw acute pain in rats.Methods Twelve male SD rats, weighing 280~320 g, were randomly divided into two groups: normal saline group (group NS), formaldehyde-induced pain group (group F), 6 rats in each group.In group F, rats were subcutaneously injected with 2% formaldehyde 50 μl into the ventral surface of right hind paw to induce periphery inflammatory pain.In group NS, rats were subcutaneously injected with normal saline into the ventral surface of right hind paw.Mechanical threshold was assessed using von Frey hairs for every ten minutes.The rat pain behavior scores were recorded for every five minutes.The thickness of skin and skin temperature were recorded for every fifteen minutes.Results Mechanical hyperalgesia were induced in group F after formalin injection into right hind paw.Compared with group NS, rat pain behavior scores were increased significantly in group F at all time points after injection, mechanical threshold were decreased significantly in group F at 10-60 min after injection, the temperature of the skin and the skin thickness were increased significantly in group F at 15-60 min after injection (P<0.05), the levels of the expression of GABAAα3 and GABAB were significantly increased in group F (P<0.05).Conclusion GABAAα3and GABAB receptors mediates formalin-induced hyperalgesia at ventrolateral portion of the PAG (vlPAG) of rats.

Influences of 4-amino-2-methy cantharidinmide on epileptiform electroencephalogram, GABA and GABAB receptor in convulsive rats / 中国药学杂志

OBJECTIVE: To investigate the anticonvulsion effect of 4-amino-2-methyl cantharidinmide (AMC) and its influences on epileptiform electroencephalogram (EcoG), contents of γ-aminobutyric acid (GABA) and GABAB receptor. METHODS: Rat model of penicillin-induced-convulsion (PIC) was established by intracortical (ic) penicillin (PNC) injection in rat motor cortex. Valproate (VPA) was used as the positive control drug. Convulsion seizure latency and racine behavior study graduations were used as indexes to evaluate the efficacy. RM6240C multi-channel biological signal collection-processing system synchronously recorded EcoG of convulsive rats after intragastric (ig) administration of AMC (25.0, 100.0 mg · kg-1). The effects on convulsion and epileptiform discharge were analyzed. The contents of GABA and the expression of GABAB receptor in the cortex and hippocampus regions of rats were determined by immunohistochemistry technique. RESULTS: AMC at the two doses and VPA could reduce epileptiform activities and discharge and prolong the latencies of epilepsy seizure, compared with the PIC group (P 0.05); compared with model control, the expression quantity of hippocampal GABAB receptor protein was significantly increased (P 0.05). GABA expression quantity in groups of larger dosage AMC and VPA were respectively higher than that in the normal group and the model group, and the GABAB receptor protein expression quantity also significantly increased (P < 0.05). CONCLUSION AMC can antagonize the convulsion seizure and inhibit the epileptiform discharge induced by penicillin in rats. The anti-convulsion mechanism of AMC is possibly related with increasing GABA content and GABAB receptor expression in cortex and the hippocampus. Copyright 2012 by the Chinese Pharmaceutical Association.

Modulation by the GABAB receptor siRNA of ethanol-mediated PKA-alpha, CaMKII, and p-CREB intracellular signaling in prenatal rat hippocampal neurons / 대한해부학회지

Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter gamma-aminobutyric acid (GABA). We studied modulation of the neurotransmitter receptor GABABR and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS. ET increased GABAB1R protein levels, but decreased protein kinase A-alpha (PKA-alpha), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5. To elucidate GABAB1R response to ethanol, we observed the effects of a GABABR agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABABR, CaMKII and p-CREB levels, whereas phaclofen decreased GABABR, CaMKII and p-CREB levels except PKA-alpha. Furthermore, when GABAB1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABAB1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.

BOTH PEPTIDERGIC AND NONPEPTIDERGIC SMALL NEURONS IN RAT DRG EXPRESS GABABR --EVIDENCE FOR PAIN REGULATION BY PRESYNAPTIC MECHANISM IN SPINAL LEVEL / 神经解剖学杂志

It has been reported that the small type of neurons in the dorsal root ganglion (DRG) play an important role in pain regulation by a presynaptic mechanism via the metabotropic type-B γ-aminobutyric acid receptors ( GABABR ). In order to understand whether the 2populations of the small type of the neurons, peptidergic and nonpeptidergic, in DRG share the same role, immunoflourescent histochemical methods and confocal laser scanning microscope were employed to investigate the expression of the GABABR in the peptidergic and nonpeptidergic small DRG neurons. The results revealed that 92% of the peptidergic and 90% of nonpeptidergic small DRG neurons express GABABR in their perikarya and central processes, which distribute in the various laminae of the spinal dorsal horn. These results suggest both the peptidergic and nonpeptidergic populations of the small neurons in the DRG share similar role in pain modulation via presynaptic mechanisms but in given laminae of the spinal dorsal horn.

Presynaptic Mechanism Underlying Regulation of Transmitter Release by G Protein Coupled Receptors

A variety of G protein coupled receptors (GPCRs) are expressed in the presynaptic terminals of central and peripheral synapses and play regulatory roles in transmitter release. The patch-clamp whole-cell recording technique, applied to the calyx of Held presynaptic terminal in brainstem slices of rodents, has made it possible to directly examine intracellular mechanisms underlying the GPCR-mediated presynaptic inhibition. At the calyx of Held, bath-application of agonists for GPCRs such as GABAB receptors, group III metabotropic glutamate receptors (mGluRs), adenosine A1 receptors, or adrenaline alpha2 receptors, attenuate evoked transmitter release via inhibiting voltage-activated Ca2+ currents without affecting voltage-activated K+ currents or inwardly rectifying K+ currents. Furthermore, inhibition of voltage-activated Ca2+ currents fully explains the magnitude of GPCR-mediated presynaptic inhibition, indicating no essential involvement of exocytotic mechanisms in the downstream of Ca2+ influx. Direct loadings of G protein beta gamma subunit (G beta gamma) into the calyceal terminal mimic and occlude the inhibitory effect of a GPCR agonist on presynaptic Ca2+ currents (IpCa), suggesting that G beta gammamediates presynaptic inhibition by GPCRs. Among presynaptic GPCRs glutamate and adenosine autoreceptors play regulatory roles in transmitter release during early postnatal period when the release probability (p) is high, but these functions are lost concomitantly with a decrease in p during postnatal development.

Expression of GABA_B recepter subunit in hippocampus and effect of its agonist after experimental epileptic rats / 临床神经病学杂志

Objective To explore the expression of Gamma-aminobutyric acid B recepter (GABABR) subunits mRNA and the effects of its agonist Baclofen in hippocampus after KA induced seizures,of experimental epileptic rats.Methods The GABABR subunits GAR1a及GAR2 mRNAs expression were determined in hippocampus of each experimental group after epileptic seizure and Baclofen interference by hybridization in situ. Results In early(6~12 h) time of KA induced epileptic rats, the mRNA levels of both receptor subunits in hippocampal formation were found downregulation widespreadly (all P

LOCALIZATION OF GABAB RECEPTOR 1 SUBTYPE IN THE RAT NERVOUS SYSTEM / 解剖学报

Objective To observe the distribution of GABAB receptor subtype 1 (GABABR1 ) in the rat nervous system. Method Immunocytochemical staining technique by using specific antibody against GABABR1 was used. Results Intensely and densely stained GABABR1-like immunoreactive neurons were observed in the V layer of cerebral cortex. islands of Calleja, caudate putamen, septohippocampal nucleus, hippocampus, basolateral amygdaloid nucleus, medial habenular nucleus, anterodorsal thalamic nucleus, mediodorsal thalamic nucleus, dorsal lateral geniculate nucleus. preoptic nuclei, supraoptic nucleus, lateral magnocellular part of paraven- tricular nucleus, anterior commisural nucleus, median eminence, arcuate nucleus, pars compacta of substantia nigra, ventral tegmental area, interpeduncular nucleus, Edinger-Westphal nucleus, mesencephalic trigeminal nucleus, locus coeruleus, nucleus of the trapezoid they, superficial layers of the caudalis subnucleus of the spinal trigeminal nucleus, dorsal motor nucleus of vagus, Purkinje cell layer of cerebellar cortex, laminae Ⅰ- Ⅲ, Ⅸ and X of spinal gray matter, lateral spinal nucleus, Onuf's nucleus and spinal dorsal root ganglion. Specially, in the cholinergic and monoaminergic nuclei of the brain. Conclusion These results indicate that GABABR1-like im- munoreactive structures are widely located in the rat brain. GABA might exert its principal inhibitory effects through these GABABR.