UMLS:C0155339 - FACTA Search

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Query: UMLS:C0155339 (Brown)
12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The amino acid, gamma-aminobutyric acid (GABA), activates two different receptor types (Bowery et al., 1980; reviewed by Ogata, 1990a). 2. GABAA receptors are bicuculline-sensitive and are coupled to Cl- channels, while activation of bicuculline-insensitive GABAB receptors has been implicated in the modulation of Ca2+ (Dunlap and Fischbach, 1981) and K+ (Gahwiler and Brown, 1985; Inoue et al., 1985a,b; reviewed by Ogata, 1990b) channels. 3. Baclofen is a specific agonist for GABAB receptors (Bowery et al., 1980). In rat sensory neurones, baclofen suppresses the membrane Ca2+ current (ICa) by a mechanism involving a partussis toxin-sensitive G protein (Holz et al., 1986; Scott and Dolphin, 1986). 4. It has been shown that the inhibitory effect of baclofen is more potent on the early portion of ICa than on the later portion and consequently the rate of ICa activation is slowed (Deisz and Lux, 1985; Dolphin and Scott, 1986). 5. The mechanisms underlying these GABAB-mediated modulation of ICa is not fully understood. This article reviews the inhibitory action of baclofen on ICa in sensory neurones.
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PMID:GABAB-mediated modulation of the voltage-gated Ca2+ channels. 132 63

The effects of helium pressure and of general anaesthetics were studied on the responses of the isolated superior cervical ganglion of the rat, to determine how far these reflected the pressure reversal of anaesthesia seen in vivo. The method of Brown & Marsh (1974) for extracellular recording of surface potentials was adapted for use in a high-pressure chamber. Helium alone, at 130 atm, did not alter the responses of the ganglion to gamma-aminobutyric acid (GABA) but significantly depressed the depolarizing and hyperpolarizing components of the nicotinic responses, and the muscarinic responses. The potentiation of the responses to GABA caused by pentobarbitone was not altered by the application of helium, at 130 atm. This pressure also decreased further the nicotinic responses which were depressed by pentobarbitone. Nitrogen, at 34 atm (the anaesthetic ED50 in vivo) and at 68 atm, significantly decreased the nicotinic responses of the ganglia, and the addition of helium to a total of 130 atm further increased this depression. At pressures of 3.3-68 atm, nitrogen caused small decreases in the responses to GABA. Nitrous oxide at 1.5 atm (the ED50 for loss of righting reflex in mice) and at 3 atm, significantly depressed the responses to GABA and to the nicotinic agonist, but did not alter the responses to methylfurmethide. The effects of nitrous oxide were unaltered when helium was added to a total of 130 atm, although this pressure of helium added alone significantly depressed the cholinergic responses. A mixture of 50% nitrous oxide and 50% oxygen, when added to the pressure chamber, at normal atmospheric pressure, caused transient increases in the responses to GABA. The effects of temperature on GABA responses and on nicotinic responses were very different from those of pressure. Preliminary evidence suggested that raising the temperature may decrease the extent of potentiation of GABA responses by pentobarbitone. The results are discussed in relation to the pressure reversal of anaesthesia in vivo. It was concluded that there was no evidence that the basis of this interaction lay in the potentiation of GABA responses by general anaesthetics, or the depression of cholinergic responses, although the changes seen were not in all cases simply additive. It was considered that effects of general anaesthetics such as the potentiation of GABA may contribute to the effects used to measure general anaesthesia in vivo, such as loss of righting reflex, but may not be related to the non-specific actions which cause anaesthesia.
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PMID:The effects of anaesthetics and high pressure on the responses of the rat superior cervical ganglion in vitro. 374 96

1 The method of Brown & Marsh (1974) for recording of surface potentials from the rat superior cervical ganglion has been adapted for use in a high pressure chamber in order to study the effects of high pressure of helium and the possible interactions with the effects of general anaesthetics. 2 Helium pressure of 130 atm did not alter the amplitude of the responses recorded from the ganglion in response to gamma-aminobutyric acid (GABA) application (9.7 and 19.4 microM) but the amplitude of responses to a nicotinic agonist were depressed. 3 Ketamine, at concentration between 18 and 180 microM, considerably potentiated the responses of the ganglion to GABA. 4 Helium pressure (130 atm) did not reverse the potentiation of GABA by ketamine. 5 The results are discussed in connection with the ability of ketamine to oppose the behavioural effects of high pressure.
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PMID:Effects of ketamine and of high pressure on the responses to gamma-aminobutyric acid of the rat superior cervical ganglion in vitro. 629 83

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.
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PMID:Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice. 902 Dec 2

Reproductive aging in the Brown Norway rat occurs because of testicular as well as hypothalamic-pituitary dysfunction. Excitatory amino acids (EAA) participate in the regulation of pulsatile secretion of hypothalamic GnRH and pituitary LH. In the present study, we studied the EAA-GnRH-LH axis for possible age-related alterations in prepubertal (35 days), young (3-4 months), middle-aged (12-13 months) and old (21-23 months) rats. In the first experiment, an intra-atrial cannula was implanted in rats of different ages to evaluate the pituitary response to small, physiological intravenous bolus administration of GnRH (0.5 or 1.0 nmol/100 g body weight). The results showed no age-related significant differences in in-vivo serum LH or FSH responsiveness to GnRH. In a second experiment, blood samples for the gonadotropins were withdrawn immediately before and 10 min after an iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg, a dose that induces a physiological LH pulse in young rats). Administration of NMDA induced significant increases in LH and prolactin in all groups of animals (P<0.05) and a significant FSH response in young and middle-aged but not old rats. NMDA-induced LH, FSH and prolactin release was higher (P<0.05) in prepubertal rats than in all other age groups. Compared with young rats, NMDA-induced increase in plasma LH and prolactin was lower (P<0.05) in old rats. In the third experiment, to ascertain whether this reduced LH response to NMDA in old rats was exerted at the hypothalamic level, the effects of NMDA on GnRH release in vitro from preoptic area-medial basal hypothalamus (POA-MBH) fragments were compared among rats of different ages. GnRH efflux in response to NMDA was significantly attenuated with increasing age. GnRH release in vitro was higher in prepubertal and lower in old than in young rats (P<0.05). Lastly, we measured amino acid concentrations in hypothalamic tissue (POA-MBH fragments). Prepubertal rats had higher levels of glutamate and taurine than young rats. Significant reductions in glutamate and gamma-aminobutyric acid (GABA) levels were found in old compared to young rats. In conclusion, these results showed that the hypothalamic NMDA-GnRH-LH axis was altered in old rats. The decreased hypothalamic content of some of the EAA and the reduced responsiveness of GnRH neurons to NMDA (both in vivo and in vitro) may contribute to an altered LH pulsatile secretion observed in old rats.
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PMID:Aging results in attenuated gonadotropin releasing hormone-luteinizing hormone axis responsiveness to glutamate receptor agonist N-methyl-D-aspartate. 953 55

Changes in the concentrations of gamma-aminobutyric acid (GABA), soluble calcium ions, glutamic acid, and the activity of glutamate decarboxylase (GAD) were investigated in non-germinated vs. germinated brown rice. Brown rice was germinated for 72 h by applying each of the following solutions: (1) distilled water, (2) 5 mM lactic acid, (3) 50 ppm chitosan in 5 mM lactic acid, (4) 5 mM glutamic acid, and (5) 50 ppm chitosan in 5 mM glutamic acid. GABA concentrations were enhanced in all of the germinated brown rice when compared to the non-germinated brown rice. The GABA concentration was highest in the chitosan/glutamic acid that germinated brown rice at 2,011 nmol/g fresh weight, which was 13 times higher than the GABA concentration in the non-germinated brown rice at 154 nmol/g fresh weight. The concentrations of glutamic acid were significantly decreased in all of the germinated rice, regardless of the germination solution. Soluble calcium and GAD were higher in the germinated brown rice with the chitosan/glutamic acid solution when compared to the rice that was germinated in the other solutions. GAD that was partially purified from germinated brown rice was stimulated about 3.6-fold by the addition of calmodulin in the presence of calcium. These data show that the germination of brown rice in a chitosan/glutamic acid solution can significantly increase GABA synthesis activity and the concentration of GABA.
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PMID:Stimulation of gamma-aminobutyric acid synthesis activity in brown rice by a chitosan/glutamic acid germination solution and calcium/calmodulin. 1278 89

In the present work we investigated the effects of brown rice extracts on proliferation and apoptosis of cancer cells. Brown rice extracts were prepared using nongerminated brown rice versus germinated brown rices. Mouse leukemia L1210 cells, human acute lymphoblastic leukemia Molt4 cells, and human cervical cancer HeLa cells were treated with either nongerminated brown rice extract (N ex), water-germinated extract (W ex), chitosan-germinated extract (C ex), glutamic acid-germinated brown rice extract (G ex), or chitosan/glutamic acid-germinated brown rice extract (CG ex). The concentrations of gamma-aminobutyric acid (GABA) in the G ex and CG ex were three and 3.3 times higher than the GABA concentration in the N ex, respectively. The G ex and CG ex retarded significantly the proliferation rates of L1210 and Molt4 cells, and the highest retardation rate was with CG ex. In addition, the G ex and CG ex enhanced significantly apoptosis of the cultured L1210 cells, but no significant apoptosis was seen with the other extracts, which have lower concentrations of GABA than G ex and CG ex. These results show that brown rice extracts with enhanced levels of GABA have an inhibitory action on leukemia cell proliferation and have a stimulatory action on the cancer cell apoptosis.
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PMID:Effects of germinated brown rice extracts with enhanced levels of GABA on cancer cell proliferation and apoptosis. 1511 48

The aging process in rodents is associated with learning and memory impairments that are correlated with changes in multiple neurotransmitter systems in the hippocampus. For example, the gamma-aminobutyric acid (GABA)ergic system is compromised in old compared with young rats (Shetty and Turner [1998] J. Comp. Neurol. 394:252-269; Vela et al. [2003] J. Neurochem. 85:368-377; Potier et al. [1992] Neuroscience 48:793-806; Potier et al. [1994] Brain Res. 661:181-188). The present study investigated the important issue of whether there is a decline of the GABAergic inhibitory system between middle and old age. Five middle-aged (15-17 months) and five old (25-29 months) Fischer 344 x Brown Norway male rats were perfused, and coronal sections through the dorsal hippocampus were immunoreacted with antibodies either to NeuN, a neuronal marker, or to the 67-kDa isoform of glutamic acid decarboxylase (GAD), the rate-limiting enzyme for GABA synthesis. Using the optical dissector technique, NeuN-immunoreactive (IR) cells, GAD-IR cells, and GAD-IR boutons were quantified stereologically in the dentate gyrus, CA3, and CA1. The resulting GAD-IR cell and GAD-IR bouton densities then were normalized to NeuN-IR cell density to exclude the possible confound of tissue shrinkage. The results revealed a significant decline in GAD-IR cells between middle and old age in CA1 but not in dentate gyrus or CA3. Interestingly, GAD-IR boutons did not show a decline in CA1, CA3, or dentate gyrus between middle and old age. It is possible that loss of CA1 inhibitory interneurons in the dorsal hippocampus contributes to the learning and memory impairments reported in old rats.
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PMID:Stereological quantification of GAD-67-immunoreactive neurons and boutons in the hippocampus of middle-aged and old Fischer 344 x Brown Norway rats. 1536 30

Obsessive-compulsive disorder (OCD) is a well-recognized severe neuropsychiatric illness. Genetic factors are believed to be important etiologically. Although historically genetic testing has focused on the serotonergic and dopaminergic systems, there is increasing evidence that the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), may also be functionally involved. Furthermore the GABA type B receptor 1 (GABBR1) gene has been localized to chromosome 6p21.3 region, which has shown linkage to OCD. We investigated five polymorphisms (A-7265G substitution; C10497G substitution; A33795G substitution in the 3'-UTR; Ser-491-Ser-T1473C transition; Phe-659-Phe-T1977C transition) in the GABBR1 gene in a sample of 159 DSM-IV OCD probands and their families, using the transmission disequilibrium test (TDT). A trend was observed with an over-transmission of -7265A allele at the A-7265G polymorphism and OCD (chi2 = 3.270, P = 0.071). Moreover, the TDT haplotype analysis using TRANSMIT showed a trend toward association with the haplotype of the five polymorphisms together [2.1.1.2.1 (A-7265G.C10497G.Ser-491-Ser.Phe-659-Phe.A33795G)] with a Chi-square value of 3.418, which corresponds to a P-value of 0.065 (overall chi2 = 6.353, 5 df, P = 0.273). Moreover, a trend was observed for the total Yale-Brown obsessive-compulsive scale score in the A-7265G polymorphism (-7265A: z = 1.934, P = 0.053) using the Family-Based Association Test, considering the diagnosis of OCD and then the clinically relevant quantitative phenotypes. The observed trends suggest that further investigations of the role of the GABBR1 gene in OCD are warranted.
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PMID:Evidence for the gamma-amino-butyric acid type B receptor 1 (GABBR1) gene as a susceptibility factor in obsessive-compulsive disorder. 1568 26

Ultrastructurally identified inhibitory synapses in layer II of rat sensorimotor cortex decline between middle and old age [Poe, B.H., Linville, C., Brunso-Bechtold, J., 2001. Age-related decline of presumptive inhibitory synapses in the sensorimotor cortex as revealed by the physical disector. J. Comp. Neurol. 439, 65-72]. The current study investigated whether a loss or shrinkage of gamma-aminobutyric acid (GABA)ergic interneurons contribute to that decline. Coronal sections from middle-aged (15-17 months) and old (25-29 months) Fischer 344 X Brown Norway male rats were immunoreacted with antibodies to the GABA synthesizing enzyme glutamic acid decarboxylase (GAD); the calcium-binding protein parvalbumin (PV), or the neuronal marker NeuN. The number of GAD-immunoreactive (IR), PV-IR, and NeuN-IR cells were determined stereologically using the optical disector technique and the cross-sectional areas of GAD-IR cells were measured in layers II/III, IV, V and VI of sensorimotor cortex. Neither the number of GAD-IR or NeuN-IR cells, nor the size of GAD-IR cells, declined significantly between middle and old age. A modest decline in the PV-IR subset of inhibitory interneurons was observed, predominantly due to changes in layers V and VI. Stereological analysis of layer II/III GAD-IR boutons revealed a stability of immunocytochemically identified inhibitory terminals. Taken together, these results indicate a general maintenance of overall GABAergic neurons in sensorimotor cortex between middle and old age and the loss of ultrastructurally identified inhibitory synapses may be due to the decline of a subset of GABAergic terminals.
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PMID:Maintenance of inhibitory interneurons and boutons in sensorimotor cortex between middle and old age in Fischer 344 X Brown Norway rats. 1672 92

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