RESUMEN
The anticonvulsant drug Gabapentin (GAB) is used for the treatment of various diseases (e.g. epilepsy, bipolar disorder, neuropathic pain) and is being consumed in high amounts. As GAB is not metabolized and shows a weak elimination in sewage treatment plants (STPs), it has been detected in surface water and even in raw potable water. Moreover, the confirmed teratogenic effects of GAB indicate the need for further investigations regarding options for the elimination of GAB in the water cycle. Little is known about the behavior of GAB during treatment with UV light, which is normally used for the disinfection of potable water and discussed for advanced wastewater treatment. In this study, GAB was exposed to polychromatic UV irradiation at different initial concentrations in aqueous solution. Afterwards the structures of the resulting phototransformation products (PTPs) were identified and elucidated by means of high-resolution mass spectrometry. GAB and photolytic mixtures were submitted to the Closed Bottle Test (CBT; OECD 301 D) to assess biodegradability. Furthermore, the toxicity of GAB and its photolytic mixtures was initially addressed on screening level using a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829). Environmentally realistic concentrations of GAB were disclosed by predicting STP influent concentrations (24.3 and 23.2 µg L(-1)). GAB with initial concentration of 100 mg L(-1) was eliminated by 80% after 128 min of direct UV irradiation, but just 9% of non-purgeable organic carbon (NPOC) was removed indicating the formation of dead-end transformation products (TPs). Structures of different PTPs were elucidated and several identical PTPs could also be identified at lower initial treatment concentrations (20 mg L(-1), 5 mg L(-1), 1 mg L(-1) and 0.1 mg L(-1)). GAB was classified as not readily biodegradable. Moreover, photo treatment did not result in better biodegradable PTPs. With increasing UV treatment duration, photolytic mixtures of GAB showed an increased inhibition of both, the bacterial luminescence emission as well as the growth in the modified LBT. In the umu-test no significant induction of the umuC gene as an indicator of genotoxicity was observed. Our results show that UV irradiation of GAB containing water would lead to the formation of recalcitrant PTPs. Considering that GAB was found in raw drinking water, the formation of toxic PTPs during drinking water treatment with UV light might be possible. Therefore, further studies should be conducted regarding the fate and effects on human health and the environment of GAB and the PTPs identified within this study.
Asunto(s)
Aminas/efectos de la radiación , Anticonvulsivantes/efectos de la radiación , Ácidos Ciclohexanocarboxílicos/efectos de la radiación , Fotólisis , Contaminantes Químicos del Agua/efectos de la radiación , Ácido gamma-Aminobutírico/efectos de la radiación , Aminas/toxicidad , Anticonvulsivantes/toxicidad , Bacterias/efectos de los fármacos , Biodegradación Ambiental , Ácidos Ciclohexanocarboxílicos/toxicidad , Gabapentina , Luminiscencia , Pruebas de Mutagenicidad , Pruebas de Toxicidad Aguda/métodos , Rayos Ultravioleta , Contaminantes Químicos del Agua/toxicidad , Ácido gamma-Aminobutírico/toxicidadRESUMEN
PURPOSE: To determine if a small ultraviolet emitting diode (UV LED) could release sufficient gamma-aminobutyric acid (GABA) from a caged precursor to suppress paroxysmal activity in rat brain slices. METHODS: Electrophysiologic recordings were obtained from rat brain slices bathed with caged GABA: 4-[[(2H-benzopyran-2-one-7-amino-4-methoxy)carbonyl]amino]butanoic acid (BC204), at concentrations between 3 and 30 microm. Seizure-like activity was induced by perfusing slices with extracellular medium lacking magnesium and containing 4-aminopyridine (4-AP; 100 microm). A small, high-power UV LED was used to uncage BC204 and determine whether an increase in ambient GABA could alter normal or paroxysmal activity in the slice. RESULTS: UV LED illumination, in the absence of BC204, had no effect on CA1 population spikes or seizure-like activity. The light did induce a small temperature elevation (<0.15 degrees C) over the current intensities and exposure durations used in these experiments. In the presence of BC204, UV light decreased the CA1 population spike and seizure-like activity. The BC204 effect can be best accounted for by release of GABA: The reduction of population spikes and seizure-like activity was blocked by the GABA antagonist picrotoxin, and BC204 illumination produced a membrane polarization that reversed at the expected potential for GABA(A) receptors. DISCUSSION: These experiments establish that illumination of a low concentration of caged GABA with a tiny UV LED can release sufficient GABA to attenuate seizure-like activity in brain slices. Because our seizure model is very severe, it is probable that this technique would have a robust effect in human focal epilepsy.
Asunto(s)
GABAérgicos/uso terapéutico , Hipocampo/efectos de la radiación , Convulsiones/prevención & control , Rayos Ultravioleta , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico , 4-Aminopiridina/farmacología , Animales , Convulsivantes/farmacología , Modelos Animales de Enfermedad , Epilepsias Parciales/tratamiento farmacológico , GABAérgicos/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Masculino , Procesos Fotoquímicos/efectos de la radiación , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/efectos de los fármacos , Receptores de GABA-A/metabolismo , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
The present work aims at developing a new process to synthesize HMX from DAPT using ultrasound in ionic liquid. Reaction has been carried out in ultrasonic bath, effect of various parameters such as presence and absence of ultrasound, volume and type of solvent, temperature, concentration of nitrating agent has been investigated with an aim of obtaining the optimum conditions for the synthesis of HMX. It was observed that ultrasonically promoted nitroylsis of DAPT to HMX has exhibited significant enhancement in yield at ambient condition.
Asunto(s)
Azocinas/química , Azocinas/efectos de la radiación , Triglicéridos/química , Triglicéridos/efectos de la radiación , Ácido gamma-Aminobutírico/análogos & derivados , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Nitratos/síntesis química , Solventes , Espectrofotometría Infrarroja , Temperatura , Ultrasonido , Ácido gamma-Aminobutírico/química , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
The therapy of focal epilepsy remains unsatisfactory for as many as 25% of patients. We tested the hypothesis that an efficient, ultraviolet light emitting diode (UV LED), coupled with a newly developed "caged" gamma-aminobutyric acid (GABA), might be capable of terminating "ictal-like" events in cultured murine neurons. GABA was released from BC204, a recently described caged GABA, using a small, ultraviolet (UV) LED. Ictal-like events were provoked by removal of extracellular magnesium. In preliminary control experiments, the concentration of GABA released from our caged compound was dependent upon the strength and duration of the illumination, and readily achieved micromolar (microM) levels that are known to activate tonic, extrasynaptic GABA(A) receptors. Ultraviolet illumination had no effect when BC204 was not present in the perfusate and the currents produced by BC204 were eliminated by picrotoxin. Within a few seconds of UV illumination, BC204 rapidly terminated ictal-like events at low microM concentration. Uncaging of BC204 also blocked the elevation of intracellular calcium induced by seizure-like discharges in our cultures. While much more technical development is clearly required to extend our observations to a more intact preparation, these results suggest the intriguing possibility of constructing an implantable device to "optically suppress" focal human seizures under closed loop control.
Asunto(s)
Anticonvulsivantes/efectos de la radiación , Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/terapia , Convulsiones/tratamiento farmacológico , Ácido gamma-Aminobutírico/análogos & derivados , Animales , Anticonvulsivantes/administración & dosificación , Calcio/metabolismo , Células Cultivadas , Electrofisiología , Antagonistas del GABA/farmacología , Hipocampo/citología , Hipocampo/efectos de los fármacos , Ratones , Microscopía Fluorescente , Neuronas/efectos de los fármacos , Picrotoxina/farmacología , Convulsiones/fisiopatología , Rayos Ultravioleta , Ácido gamma-Aminobutírico/administración & dosificación , Ácido gamma-Aminobutírico/efectos de la radiación , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
BACKGROUND: CNS-irradiation in prepubertal children with leukemia or brain tumors can lead to precocious or in high doses to delayed puberty. The underlying mechanisms of these disorders are unknown. METHODS: A new animal model of experimentally induced pubertal disorders by cranial irradiation has been developed. In infantile or juvenile (12 - 23 days old) female rats precocious or delayed puberty have been induced by selective cranial Co60-irradiation (4 - 18 Gy). At age of 32 - 38 days or 3 months relevant hormone parameters have been studied basal and after stimulated conditions. RESULTS: Low radiation doses (5 or 6 Gy) led to accelerated onset of puberty as well as elevated LH- and estradiol levels. High radiation doses (9 - 18 Gy) caused retardation of sexual development, lower gonadotropin levels and growth retardation associated with growth hormone deficiency. After cranial irradiation with 5 Gy the release rates of the inhibitory neurotransmitter gamma-aminobutyric-acid (GABA) from hypothalamic explants were significantly lower (p < 0,05). The gonadotropin-releasing-hormone (GnRH) expression in the hypothalamic preoptic area of irradiated animals (5 Gy) was significantly higher than in controls (p < 0,05). CONCLUSION: The GnRH-pulse generator is very radiosensitive as low dose irradiation causes precocious puberty, whereas high dose irradiation is associated with delayed sexual maturation. Radiation induced precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to desinhibition and premature activation of GnRH neurons. Our animal model of cranial irradiation seems to be suitable to study neurotransmitter disorders, molecular mechanisms and potential preventive intervention of radiation induced pubertal changes.
Asunto(s)
Anomalías Inducidas por Radiación , Encéfalo/efectos de la radiación , Hormona Liberadora de Gonadotropina/efectos de la radiación , Ácido gamma-Aminobutírico/efectos de la radiación , Factores de Edad , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Hormona Liberadora de Gonadotropina/deficiencia , Neuronas/efectos de la radiación , Pubertad Tardía/etiología , Pubertad Precoz/etiología , Dosis de Radiación , Ratas , Ratas Sprague-DawleyRESUMEN
Brain irradiation in prepubertal children with malignomas can cause precocious puberty. A selective cranial cobalt (Co(60))-irradiation technique has been developed in rats. In two experiments early juvenile (13-15 days old) female rats received a single dose of 5 Gy or sham irradiation. At pubertal age (post-natal days 33-34) irradiated rats had higher serum estradiol and luteinizing hormone levels. In experiment 1 irradiated rats had higher gonadotropin releasing-hormone (GnRH) mRNA levels in the preoptic area compared to controls (P<0.05). In experiment 2 the release rates of gamma-aminobutyric acid (GABA) in vitro from preoptic mediobasal hypothalamic areas of irradiated rats were significantly reduced after stimulation with the GABA(A) receptor agonist muscimol (maximum values 4607+/-804 vs. 7399+/-1048 pM in controls, mean+/-SEM, P<0.05). Radiation induced central precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to premature activation of the GnRH-pulse generator.
Asunto(s)
Hormona Liberadora de Gonadotropina/efectos de la radiación , Hipotálamo/efectos de la radiación , Neuronas/efectos de la radiación , Hipófisis/efectos de la radiación , Pubertad Precoz/metabolismo , Ácido gamma-Aminobutírico/efectos de la radiación , Animales , Femenino , Expresión Génica/fisiología , Expresión Génica/efectos de la radiación , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Neuronas/metabolismo , Hipófisis/metabolismo , Pubertad Precoz/etiología , ARN Mensajero/metabolismo , ARN Mensajero/efectos de la radiación , Ratas , Transmisión Sináptica/efectos de la radiación , Ácido gamma-Aminobutírico/metabolismoRESUMEN
It had been found that both the single prolonged irradiation and chronic (fractionated) one with doses of 25 and 50 cGy (1.75 mGy/min) caused essential modification of the biphase modulative effects of acetylcholine and gamma-aminobutyric acid upon K+ level in rat brain cortex slices to be compared to the acute lethal irradiation influence. The results of model experiments showed saturated fatty acids to be significant for the changes in regulative functions of nerve cell membranes after exposure to low dose-rate radiation.
Asunto(s)
Encéfalo/efectos de la radiación , Neurotransmisores/efectos de la radiación , Acetilcolina/farmacología , Acetilcolina/efectos de la radiación , Animales , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Iones , Masculino , Neurotransmisores/farmacología , Potasio/metabolismo , Potasio/efectos de la radiación , Ratas , Ratas Wistar , Factores de Tiempo , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
[equation--see text] Introducing 3-methoxy or 3,5-dimethoxy substituents on the 4-hydroxyphenacyl (pHP) photoremovable protecting group has been explored with two excitatory gamma-amino acids, L-glutamic acid and gamma-amino butyric acid (GABA). These substituents significantly extend the absorption range of the pHP chromophore, e.g., the tail of absorption bands of 2a,b extend above 400 nm, well beyond the absorptions of aromatic amino acids and nucleotides. Irradiation releases the amino acids with rate constants of approximately 10(7) s(-)(1) and appearance efficiencies (Phi(app)) of 0.03-0.04. The photoproducts are formed through the pHP excited triplet and are primarily products of photoreduction and photohydrolysis. 1a,b also rearranged to the phenylacetic acid 3.
Asunto(s)
Fotólisis , Acetofenonas/química , Acetofenonas/efectos de la radiación , Animales , Bicuculina/farmacología , Conductividad Eléctrica , Electrones , Ácido Glutámico/química , Ácido Glutámico/farmacología , Ácido Glutámico/efectos de la radiación , Hipocampo/citología , Canales Iónicos/efectos de los fármacos , Luz , Mediciones Luminiscentes , Neuronas/efectos de los fármacos , Neuronas/fisiología , Neuronas/efectos de la radiación , Ratas , Ácido gamma-Aminobutírico/química , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
High levels of activity at a synapse can lead to spillover of neurotransmitter from the synaptic cleft. This extrasynaptic neurotransmitter can diffuse to neighboring synapses and modulate transmission via presynaptic receptors. We studied such modulation at the synapse between granule cells and Purkinje cells in rat cerebellar slices. Brief tetanic stimulation of granule cell parallel fibers activated inhibitory neurons, leading to a transient elevation of extracellular GABA, which in turn caused a short-lived heterosynaptic depression of the parallel fiber to Purkinje cell EPSC. Fluorometric calcium measurements revealed that this synaptic inhibition was associated with a decrease in presynaptic calcium influx. Heterosynaptic inhibition of synaptic currents and calcium influx was eliminated by antagonists of the GABAB receptor. The magnitude and time course of the depression of calcium influx were mimicked by the rapid release of an estimated 10 microM GABA using the technique of flash photolysis. We found that inhibition of presynaptic calcium influx peaked within 300 msec and decayed in <3 sec at 32 degrees C. These results indicate that presynaptic GABAB receptors can sense extrasynaptic GABA increases of several micromolar and that they rapidly regulate the release of neurotransmitter primarily by modulating voltage-gated calcium channels.
Asunto(s)
Corteza Cerebelosa/fisiología , Receptores de GABA-B/fisiología , Transmisión Sináptica/fisiología , Ácido gamma-Aminobutírico/fisiología , Animales , Calcio/metabolismo , Canales de Calcio/metabolismo , Corteza Cerebelosa/citología , Estimulación Eléctrica , Antagonistas del GABA/farmacología , Transporte Iónico , Cinética , Técnicas de Placa-Clamp , Fenilacetatos/metabolismo , Fenilacetatos/efectos de la radiación , Fotólisis , Células de Purkinje/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de GABA-B/efectos de los fármacos , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
Three groups of rats (intact, irradiated with 30 Gy of gamma rays and treated after irradiation with the use of pharmacological and metabolic drugs protecting brain against hypoxia were studied. In 24 hours after the influence the animals have undergone the neurobehavioral testing and then were sacrificed, a number of neurochemical parameters depicting energy metabolism and metabolic GABA bypath in brain were studied (general number of parameters were 24). Using classical method of t-statistics only enhancement of labelled GABA catabolism and deterioration of general behavioral activity were verified, the modifying effect of the pharmacological and metabolic protection against hypoxia was not found. Using methods of multidimensional evaluation the protective and sanogenic character of the used method of therapy was verified. Thus, using discrimination analysis (Mahalanobis criterion) high similarity of intact and treated groups of animals was estimated. It was confirmed using methods of coupled and multiple correlation and method of route coefficients. The statistical connections between neurochemical and neurobehavioral parameters were found which can be useful for understanding of the mechanisms of the early postradiation syndrome development.
Asunto(s)
Hipoxia Encefálica/tratamiento farmacológico , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Animales , Conducta Animal/efectos de la radiación , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Evaluación Preclínica de Medicamentos , Femenino , Hipoxia Encefálica/epidemiología , Hipoxia Encefálica/etiología , Hipoxia Encefálica/metabolismo , Análisis Multivariante , Dosis de Radiación , Traumatismos Experimentales por Radiación/complicaciones , Traumatismos Experimentales por Radiación/epidemiología , Traumatismos Experimentales por Radiación/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Irradiación Corporal Total/efectos adversos , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
From experiments in mice, it is shown that with a radiation dose of 8 Gy (LD96) the radioprotective effect was exerted by gamma-aminobutyric acid (GABA), substances that increase its concentration in tissues (progabide and valproate), and synthetic agonists of both receptor types, particularly baclofen, a GABA-receptor agonist. The radioprotective effect is also exerted by gamma-hydroxybutyrate, not piracetam.
Asunto(s)
Piracetam/uso terapéutico , Protectores contra Radiación/uso terapéutico , Oxibato de Sodio/uso terapéutico , Ácido gamma-Aminobutírico/efectos de los fármacos , Ácido gamma-Aminobutírico/efectos de la radiación , Animales , Distribución de Chi-Cuadrado , Evaluación Preclínica de Medicamentos , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Traumatismos Experimentales por Radiación/mortalidad , Traumatismos Experimentales por Radiación/prevención & controlRESUMEN
A study was made of the effect of X-rays (4,5 Gy) and pyridoxal phosphate (3 mg/kg, v/v) on the activity of pyridoxal enzymes of GABA metabolism (e.g. glutamate decarboxylase, E.C. 4.1.1.15) and aminobutyrate aminotransferase (GABA-T, E.C. 2.6.1.19), as well as on GABA and glutamate content of the hemisphere cortex, brain stem and cerebellum of rabbits 6 and 10 days following irradiation and injection of a coenzyme. The height of the radiation sickness in rabbits was characterized by the manifest changes in glutamate decarboxylase and GABA-T activity, as well as in GABA and glutamate content of various brain parts differing in the structural and functional functions. The administration of pyridoxal phosphate produced pronounced activation of glutamate decarboxylase, particularly 6 days after irradiation and administration of the co-enzyme, and, to a lesser extent, influenced GABA-T function. Pyridoxal phosphate favored maintaining the GABA level above the control level in the hemisphere cortex and brain stem 6 and 10 days after exposure. The injection of pyridoxal phosphate did not normalize the glutamate content of the brain parts 6 days after exposure, but favored the normalization of GABA-T activity on day 10.
Asunto(s)
Encéfalo/efectos de los fármacos , Fosfato de Piridoxal/farmacología , Ácido gamma-Aminobutírico/efectos de los fármacos , Animales , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Femenino , Glutamato Descarboxilasa/efectos de los fármacos , Glutamato Descarboxilasa/metabolismo , Glutamato Descarboxilasa/efectos de la radiación , Glutamatos/efectos de los fármacos , Glutamatos/metabolismo , Glutamatos/efectos de la radiación , Ácido Glutámico , Masculino , Conejos , Traumatismos Experimentales por Radiación/metabolismo , Factores de Tiempo , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
Some biochemical disorders in the animals' central nervous system mainly in brain have been analysed after the exposure to superlethal doses of ionizing radiation as well in a state of the so-called early transient incapacity. The metabolism of gamma-aminobutyric acid, ammonia, histamine, cyclic nucleotides, prostaglandins and other biologically active substances is compared. Their investigation as metabolic regulators and modulators for nerve tissue seems to be of particular importance for deciphering the molecular mechanisms of changes in the central nervous system functional state and for discovering the possibility of its maintaining at a given level of activity.
Asunto(s)
Sistema Nervioso/efectos de la radiación , Amoníaco/metabolismo , Amoníaco/efectos de la radiación , Animales , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Histamina/metabolismo , Histamina/efectos de la radiación , Sistema Nervioso/metabolismo , Nucleótidos Cíclicos/metabolismo , Nucleótidos Cíclicos/efectos de la radiación , Prostaglandinas/metabolismo , Prostaglandinas/efectos de la radiación , Dosis de Radiación , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
The contents of gamma-aminobutyric acid (GABA) and glutamate (GL) as well as GABA-aspartate- and alanine aminotransferase activities were measured in rat cerebellum, cerebral cortex and truncus cerebri 1, 3, 6, 24 and 48 hr following total-body gamma-irradiation (60Co) with a dose of 30 Gy. All the indices under study changed in a similar way in the cortex and truncus cerebri while in the cerebellum, GABA level increased and GABA-alpha-ketoglutarate aminotransfearse activity decreased 60 min after irradiation. The levels of GABA and GL in the cortex and truncus cerebri decreased immediately and increased 24 hr after irradiation. Activity of aminotransferases changed in a phase manner: changes in aspartate- and alanine aminotransferase activity were more pronounced than those of GABA-alpha-ketoglutarate aminotransferase activity and correlated with the glutamate level changes.
Asunto(s)
Encéfalo/efectos de la radiación , Glutamatos/efectos de la radiación , Transaminasas/efectos de la radiación , Irradiación Corporal Total , Ácido gamma-Aminobutírico/efectos de la radiación , Animales , Encéfalo/metabolismo , Rayos gamma , Masculino , Dosis de Radiación , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The radioactive ligands, [3H]dihydroalprenolol and [3H]muscimol, were used to estimate the condition of beta-adrenoreceptors of the brain cortex and GABA-receptors of the cerebellum during transient neurologic disorders caused by irradiation of rats with high-energy (20 MeV) electrons of 200 Gy. No significant changes were observed in the GABA-ergic brain system while the changes in beta-adrenoreceptors of the brain were pronounced and manifested by the loss by the receptors of their ability to bind the specific ligand, dihydroalprenolol. The changes observed were reversible and correlated with the development of neurologic disorders.
Asunto(s)
Encéfalo/efectos de la radiación , Receptores Adrenérgicos beta/efectos de la radiación , Receptores de Superficie Celular/efectos de la radiación , Ácido gamma-Aminobutírico/efectos de la radiación , Animales , Cerebelo/efectos de la radiación , Corteza Cerebral/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Electrones , Ligandos , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/metabolismo , Traumatismos por Radiación/metabolismo , Ratas , Ratas Endogámicas , Receptores de GABA-ARESUMEN
Studies have been made of the effect of changes in illumination levels on 14C + GABA efflux in the isolated retina of the frog R. ridibunda. When the retina loaded with 14C-GABA is stimulated by darkness, the efflux of radioactivity immediately increases. After reaching a peak, the efflux of 14C-GABA slightly decreases attaining steady level which is higher than the level of spontaneous efflux observed during weak (approximately 0.05 lux) illumination. This high level is preserved as long as the retina remains in darkness. During illumination of the retina (transition from darkness to 60 lux), two types of response are observed. In some cases, insignificant increase of GABA efflux from the retina is followed by its rapid decrease up to the level which is observed during weak illumination. In other cases, immediately after illumination the decrease in GABA efflux takes place (in 6 experiments out of 10). In accordance with the data of Voaden [6], it is suggested that 14C + GABA is liberated from horizontal and amacrine cells. The data obtained in the present investigation are discussed in terms of Trifonov [14] and Byzov [15] hypothesis. These data confirm the idea that GABA acts as a retinal neurotransmitter in the frog.