Distribution and Pharmacological Properties of the GABA_A/ Benzodiazepine/Chloride Ionophore Receptor Complex in the Brain of the Fish Anguilla anguilla

Abstract

In the present study, we characterized the distribution and the pharmacological properties of the different components of the GABAA receptor complex in the brain of the eel (Anguilla anguilla). Benzodiazepine recognition sites labeled "in vitro" with [3H]flunitrazepam ([3H]FNT) were present in highest concentration in the optic lobe and in lowest concentration in the medulla oblongata and spinal cord. A similar distribution was observed in the density of gamma-[3H]aminobutyric acid ([3H]GABA) binding sites. GABA increased the binding of [3H]FNT in a concentration-dependent manner, with a maximal enhancement of 45% above the control value, and, vice versa, diazepam stimulated the binding of [3H]GABA to eel brain membrane preparations. The density of benzodiazepine and GABA recognition sites and their reciprocal regulation were similar to those observed in the rat brain. In contrast, the binding of the specific ligand for the Cl- ionophore, t-[35S]butylbicyclophosphorothionate ([35S]TBPS), to eel brain membranes was lower than that found in the rat brain. In addition, [35S]TBPS binding in eel brain was less sensitive to the inhibitory effects of GABA and muscimol and much more sensitive to the stimulatory effect of bicuculline, when compared with [35S]TBPS binding in the rat brain. Moreover, the uptake of 36Cl- into eel brain membrane vesicles was only marginally stimulated by concentrations of GABA or muscimol that significantly enhanced the 36Cl- uptake into rat brain membrane vesicles. Finally, intravenous administration of the beta-carboline inverse agonist 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methyl ester (20 mg/kg) and of the chloride channel blocker pentylenetetrazole (80 mg/kg) produced convulsions in eels that were antagonized by diazepam at doses five to 20 times higher than those required to produce similar effects in rats. The results may indicate a different functional activity of the GABA-coupled chloride ionophore in the fish brain as compared with the mammalian brain.

Species dependent effects of dihydroergosine on [3H]TBOB binding to membranes from the human, rat, bovine and mouse brain

“…Species differences in biochemical and pharmacological properties of the brain GABA/benzodiazepine/C1-channel receptor complex have already been documented in several studies (Rauh etal., 1990;Mann and Enna, 1980;Corda et al, 1989). These studies almost exclusively demonstrated differences between invertebrates and vertebrates suggesting that this receptor complex has been conserved over vertebrate evolution.…”

Gamma aminobutyric acid radioreceptor-assay a possible biomarker for human exposure to certain agrochemicals

“…The fish as member of the lower vertebrates was reported to have lower affinity in its GABA A receptor towards TBPS. Corda et al, (1989) found that the eel brain GABA A receptor has relatively lower binding affinity with TBPS. They concluded that the mammalian species brain is generally characterized by the high binding affinity of TBPS with in their GABA A receptor.…”

Autoradiographic localization and binding study of benzodiazepines receptor sites in carp brain (Cyprinus carpio L.)

“…Only one population of benzodiazepine recognition sites was found in the whole eel brain. In particular, Corda et al (1989) described the highest concentration of BZ binding sites in the optic lobe and the lowest in the medulla oblongata and spinal cord. In the Atlantic salmon, immunocytochemical investigations, using a monoclonal antibody against the GABA-receptor b 2 /b 3 subunits, revealed immunoreactivity in all parts of the brain (Anzelius et al, 1995).…”

“…Subsequently, the distribution and pharmacological properties of the different components of the GABA A receptor complex in the brain of the eel were extensively investigated (Corda et al, 1989). Only one population of benzodiazepine recognition sites was found in the whole eel brain.…”