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Biomedical subjects

G Biggio

Publications and source records attributed to G Biggio.

At least 181 records · Page 10Linked to original sources
PubMed1984

Stress and beta-carbolines decrease the density of low affinity GABA binding sites; an effect reversed by diazepam.

Cerebral cortex membranes from rats habituated to manipulations preceding decapitation (habituated rats) had 40% higher GABA binding than membranes from naive animals. Diazepam (5 X 10(-6) M), added to membranes from naive rats, increased GABA binding to the level of habituated rats, but failed to induce any further increase in membranes from the latter animals. Vice versa, beta-carbolines (FG 7142, beta-CCE, DMCM) added to membranes from habituated rats lowered GABA binding to the level of naive animals, but caused no further decrease in the membranes from this last group. Diazepam removed the effect of beta-carbolines in membranes from habituated rats. It is suggested that handling represents a stressful stimulus for naive animals and that stress lowers GABA binding by releasing an endogenous ligand for benzodiazepine receptors possessing similar properties to beta-carbolines. Finally, the results indicate that the emotional status of animals from which brain tissue is obtained should be considered when connections between GABA and benzodiazepine receptors are studied.

Animals↗
PubMed1984

Evidence for an involvement of GABA receptors in the mediation of the proconvulsant action of ethyl-beta-carboline-3-carboxylate.

The kinetic characteristics of binding of [3H]-GABA and the pattern of isoniazid-induced convulsions were studied in rats treated with repeated intraventricular injections of ethyl-beta-carboline-3-carboxylate (beta-CCE) (10 micrograms/rat, twice daily for 8 days). Thirty-six hours after the last injection, the total number of binding sites for [3H]-GABA was decreased (25%) in the cerebral cortex and hippocampus. On the other hand, there was no significant difference in the dissociation constant (KD) between beta-CCE and solvent-treated rats. The decrease in binding sites for [3H]-GABA was paralleled by a strong potentiation of the convulsant pattern elicited by isoniazid. The results suggest that the proconvulsant effect elicited by beta-CCE is mediated by the decrease in the total number of binding sites for GABA, secondary to the interaction between beta-CCE and the benzodiazepine receptor coupled to the GABA receptor.

Animals↗
PubMed1983

beta-Carbolines activate neurons in the substantia nigra pars reticulata: an effect reversed by diazepam and Ro15-1788.

Diazepam (0.5 mg/kg i.v.) was found to inhibit the firing rate of substantia nigra pars reticulata (SN-PR) cells by 50%. In contrast, beta-CCM, at the doses of 125 and 250 micrograms/kg i.v. increased the firing rate by 90 and 150%, respectively, while DMCM produced similar increases at doses of 250 and 500 micrograms/kg i.v. Both beta-carboline-induced excitation and diazepam-induced inhibition were reversed to baseline values by the specific antagonist of benzodiazepine recognition sites, Ro15-1788 (2.0 mg/kg i.v.). Moreover, the stimulant effect of beta-carbolines was also reversed by diazepam (1.0 mg/kg) to about 50% of baseline. The results indicate that beta-carbolines specifically influence the activity of SN-PR cells through a mechanism opposite to that of benzodiazepines themselves, acting on benzodiazepine recognition sites.

Animals↗
PubMed1983

Increase of cyclic GMP in cerebellum by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM).

The intraperitoneal administration of DMCM (0.5-3 mg/kg) produced a dose-related increase in the content of cyclic GMP in the rat cerebellar cortex. The effect of DMCM on cyclic GMP was abolished by pretreatment with benzodiazepine receptor ligands, diazepam and Ro15-1788 and by the GABA agonist muscimol. The results suggest that DMCM increases cerebellar cyclic GMP content through a direct action on benzodiazepine receptors located in the cerebellar cortex. The interaction between DMCM and the GABAergic system associated with benzodiazepine receptors is discussed. Cerebellar cyclic GMP content can be used as a biochemical index to differentiate agonists and antagonists for benzodiazepine receptors.

Animals↗
PubMed1983

Effect of a vitamin A-free diet on [3H]diazepam and [3H]GABA binding in the rat retina.

Benzodiazepine and GABA binding sites in the rat retina are influenced by a vitamin A-free diet. In rats fed a vitamin A-free diet, the total number of [3H]GABA and [3H]diazepam binding sites was markedly higher than in rats given a balanced diet. No differences were found in the apparent affinities of [3H]GABA and [3H]diazepam for their specific binding sites. The results suggest that GABA and benzodiazepine binding sites have a role in the function of the retina.

Animals↗
PubMed1983

Brain benzodiazepine receptors increase after chronic ethyl-beta-carboline-3-carboxylate.

Rats were treated with repeated intraventricular injections of ethyl-beta-carboline-3-carboxylate (beta-CCE) (10 micrograms/rat, twice daily for 8 days), 36 h after the last injection, the total number of 3H-diazepam binding sites was increased in the cerebral cortex, cerebellum and hippocampus by 63, 51 and 38%, respectively. On the other hand, there were no significant differences in the dissociation constants (KD) between beta-CCE and solvent treated rats. In contrast, chronic beta-CCE administration failed to change the number of the apparent affinity of 3H-beta-CCE binding sites in all the brain areas examined. The results suggest that beta-CCE is an antagonist at the 3H-diazepam binding sites.

Animals↗
PubMed1983

Biochemical changes in the rat cerebellar cortex elicited by chronic treatment with methyl mercury.

Long-term (20 days) treatment with methyl mercury (MeHg) increases the total number of benzodiazepine binding sites and decreases essentially the content of cyclic GMP in the cerebellar cortex. In contrast, this treatment fails to modify the content of GABA and cyclic AMP, GAD activity and GABA binding sites in the same brain area. The changes in cyclic GMP and benzodiazepine binding sites in the cerebellar cortex are discussed in relation to the motor disturbances associated with MeHg intoxication.

Animals↗
PubMed1982

Age-related changes of benzodiazepine and GABA binding sites in the rat retina.

The changes in the number and sensitivity of benzodiazepine and GABA binding sites in the rat retina during postnatal development, adulthood and ageing and their functional relationship at different ages have been studied. Data indicate an increase in the total number of both GABA and benzodiazepine binding sites with age. In contrast, the activation of retinal benzodiazepine receptor binding by GABA is significantly reduced in aged rats with respect to young adult and newborn rats. Moreover, the activation of retinal benzodiazepine receptor binding induced by dark exposure of the animals is present in young adult rats but is lost in aged rats. These results suggest that in the retina of aged rats there is an increase of GABA and benzodiazepine receptors which have lost their functional connection.

Aging↗
PubMed1981

Rapid changes in GABA binding induced by stress in different areas of the rat brain.

Rats habituated to handling preceding sacrifice have higher [3H]GABA receptor binding in different brain areas (cerebellum, frontal cortex, caudate nucleus) than naive animals. The increase in GABA binding in handling-habituated rats is due to an increase in the number of receptors (Bmax) with no changes in the affinity of GABA binding for its ligand (Kd). Foot shock causes a sudden fall in GABA binding in handling-habituated rats but does not, or only slightly, in naive ones. The results indicate that stress causes a rapid decrease in GABA receptor binding in the central system and that the GABA binding values which are usually considered as normal are, in fact, values decreased by the handling manoeuvers preceding sacrifice.

Animals↗
PubMed1981

Methyl mercury enhances [3H]diazepam binding in different areas of the rat brain.

Three days after the acute oral administration of methyl mercury (MeHg), a 27-60% increase in the total number of binding sites for [3H]diazepam was seen in the retina and different areas of the rat brain, with no change, except in the retina, in the apparent dissociation constant for its ligand. In contrast, MeHg failed to change [3H]spiroperidol and [3H]GABA binding in the same areas. Moreover, MeHg decreased cyclic GMP content in the cerebellar cortex. The various possible mechanisms involved in the action of MeHg on benzodiazepine binding are discussed.

Animals↗
PubMed1981

Denervation supersensitivity for benzodiazepine receptors in the rat substantia nigra.

The injection of kainic acid into the substantia nigra causes, 3 weeks after treatment, a 40% decrease in the total number of binding sites for [3H]diazepam with an increase in the dissociation constant. This decrease was restored to approximately normal by the subsequent injection of kainic acid into the striatum, homolateral to the lesioned substantia nigra. The injection of kainic acid into the striatum of intact animals failed to modify the number of [3H]diazepam binding sites but increased the KD. The results indicate that benzodiazepine binding sites in the substantia nigra are partly located on kainic acid sensitive elements (probably interneurons) and, partly, on kainic acid resistant ones. These binding sites become supersensitive after degeneration of striato-nigral pathways. The possible role of GABAergic denervation of the substantia nigra in the development of benzodiazepine binding sites supersensitivity is discussed.

Animals↗
PubMed1981

Kainic acid-induced lesion of rat retina: differential effect on cyclic GMP and benzodiazepine and GABA receptors.

Intraocular injection of kainic acid caused a marked decrease in GABA content in the rat retina and the almost complete loss of GAD activity in this tissue, within 3 days. Moreover, kainic acid produced a decrease of approximately 65% in the number of both [3H]diazepam and [3H]GABA binding sites without changing the apparent dissociation constants for their ligands. In contrast to that in brain areas, cyclic GMP content in the retina is neither influenced by kainic acid nor by the systemic administration of diazepam and muscimol.

Animals↗
PubMed1981

Functional interaction between benzodiazepine and GABA recognition sites in aged rats.

The present study was undertaken to explore whether there may be age-related changes in benzodiazepine binding and in the functional interaction between GABA and benzodiazepine recognition sites. Data indicate an increase in benzodiazepine binding sites with age. Moreover the functional interactions between GABA and benzodiazepine receptor sites are differentially affected by aging. GABA is less active in enhancing benzodiazepine binding in the older animals because of the loss of GABA receptors, and Diazepam may be more active in enhancing GABA receptor binding in the aged animals because there are more benzodiazepine receptors in this group. An understanding of the relevance of the apparent alteration in coupling between GABA and benzodiazepine receptors must permit a better definition of the behavioral manifestation of their biochemical phenomenon.

Aging↗