The noradrenergic modulation of endogenous γ-aminobutyric acid (GABA) outflow from slices and synaptosomes prepared from human cerebral cortex biopsies has been studied. GABA outflow was responsive to depolarizing stimuli such as ouabain and high potassium. Basal GABA outflow in slices, but not in synaptosomes, appeared to be largely dependent upon neuronal activity, being prevented by tetrodotoxin (TTX). 10 mM K+-evoked outflow in synaptosomes also proved to be TTX sensitive. Norepinephrine (NE) concentration dependently increased basal GABA outflow both in slices and synaptosomes. This effect wasα1-adrenoreceptor-mediated because it was prevented by a selective antagonist of theα1-adrenoreceptor class (prazosin) but not by theα1 antagonist idazoxan. However, andα1-mediated inhibitory modulation was also present in the preparations used, since (1) in slices, NE significantly inhibited GABA outflow in the presence of prazosin; (2) in synaptosomes, NE significantly inhibited 10 mM K+-evoked outflow in the presence of prazosin. Both of these effects were prevented by idazoxan. No β-adrenoreceptor modulation could be demonstrated. A comparison between species was also conducted. The response to ouabain and to TTX proved similar in human, rat and guinea-pig cerebral cortex. In the most simple tissue preparation used (synaptosomes), a close similarity between the three species could be observed. In all species, NE stimulated basal GABA outflow, an effect prevented by prazosin. This suggests a predominantα1-adrenoreceptor-mediated stimulatory effect. In a more complex preparation (slices), differences between species could be demonstrated. First, in absolute values basal GABA outflow was higher in the rat compared to the human and the guinea-pig cortex. Second, although NE stimulated GABA outflow viaα1-adrenoreceptors in all species, it wa more potent in the rat. Third, in the presence of prazosin NE significantly inhibited basal GABA outflow in the human cortex, but not in the other species. This suggests that the representation of functionalα2-adrenoreceptors (on the cell bodies of GABA neurones and /or other connected neuronal populations) is greater in the human when compared to the rat and the guinea-pig cerebral cortex.
Noradrenergic modulation of gamma-aminobutyric acid outflow from the human cerebral cortex.
FERRARO, Luca Nicola;TANGANELLI, Sergio;CALO', Girolamo;ANTONELLI, Tiziana;BIANCHI, Clementina;BEANI, Lorenzo;SIMONATO, Michele
1993
Abstract
The noradrenergic modulation of endogenous γ-aminobutyric acid (GABA) outflow from slices and synaptosomes prepared from human cerebral cortex biopsies has been studied. GABA outflow was responsive to depolarizing stimuli such as ouabain and high potassium. Basal GABA outflow in slices, but not in synaptosomes, appeared to be largely dependent upon neuronal activity, being prevented by tetrodotoxin (TTX). 10 mM K+-evoked outflow in synaptosomes also proved to be TTX sensitive. Norepinephrine (NE) concentration dependently increased basal GABA outflow both in slices and synaptosomes. This effect wasα1-adrenoreceptor-mediated because it was prevented by a selective antagonist of theα1-adrenoreceptor class (prazosin) but not by theα1 antagonist idazoxan. However, andα1-mediated inhibitory modulation was also present in the preparations used, since (1) in slices, NE significantly inhibited GABA outflow in the presence of prazosin; (2) in synaptosomes, NE significantly inhibited 10 mM K+-evoked outflow in the presence of prazosin. Both of these effects were prevented by idazoxan. No β-adrenoreceptor modulation could be demonstrated. A comparison between species was also conducted. The response to ouabain and to TTX proved similar in human, rat and guinea-pig cerebral cortex. In the most simple tissue preparation used (synaptosomes), a close similarity between the three species could be observed. In all species, NE stimulated basal GABA outflow, an effect prevented by prazosin. This suggests a predominantα1-adrenoreceptor-mediated stimulatory effect. In a more complex preparation (slices), differences between species could be demonstrated. First, in absolute values basal GABA outflow was higher in the rat compared to the human and the guinea-pig cortex. Second, although NE stimulated GABA outflow viaα1-adrenoreceptors in all species, it wa more potent in the rat. Third, in the presence of prazosin NE significantly inhibited basal GABA outflow in the human cortex, but not in the other species. This suggests that the representation of functionalα2-adrenoreceptors (on the cell bodies of GABA neurones and /or other connected neuronal populations) is greater in the human when compared to the rat and the guinea-pig cerebral cortex.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
