Abstract
Somatostatin has been reported to modulate GABAA receptor complex in many brain structures. This study was conducted to investigate somatostatin modulation of the GABAA receptor binding in several rat diencephalic structures, focusing primarily on the thalamus, as this structure plays important roles. Animals were assigned to control conditions. Changes in specific binding of GABAA receptor as labelled with [35S]t-Butylbicyclophosphorothionate (TBPS) were assessed by in vitro quantitative autoradiography with the aid of a computer assisted image analysis system. Our results reveal the presence of higher densities in several thalamic structures located principally in the part of thalamus. We demonstrate for the first time the presence of a modulatory effect of somatostatin on the GABAA receptor complex in this brain region in rats. Indeed, the peptide affected in a concentration-dependent manner; the binding of [35S]-Tertiary Butylbicyclophosphorothionate (TBPS) to the convulsant site of the GABAA receptor complex in thalamic structures with an affinity in the micromolar range (10-3 to 3.10-6M). The inhibitory effect of somatostatin is observed in all thalamic structures analyzed. The absence of a specific region effect of somatostatin on the binding of [35S]-TBPS, suggests the presence of a homogenous subunit GABAA receptor composition. Furthermore, GABA and muscimol, a GABAA receptor agonist, enhanced the affinity of somatostatin effect on [35S]-TBPS. This suggests that somatostatin allosterically modifies [35S]-TBPS binding through a mechanism similar to that of GABA.
Highlights
Gamma-Amino Butyric Acid (GABA) is widely accepted as an inhibitory neurotransmitter in the mature central nervous system (Purves et al, 2012; Bowery and Smart, 2006)
GABA and muscimol, a GABAA receptor agonist, enhanced the affinity of somatostatin effect on [35S]-Tertiary Butylbicyclophosphorothionate (TBPS). This suggests that somatostatin allosterically modifies [35S]-TBPS binding through a mechanism similar to that of GABA
Under the experimental conditions used in this investigation, somatostatin inhibited [35S]-TBPS specific binding in a dose-dependent manner in the rat thalamic structures (Fig. 1)
Summary
Gamma-Amino Butyric Acid (GABA) is widely accepted as an inhibitory neurotransmitter in the mature central nervous system (Purves et al, 2012; Bowery and Smart, 2006). GABAA are hetero-oligomeric ligand-gated ion channel proteins They are distributed widely in the central nervous system of many vertebrate species (Edgar and Schwartz, 1990; Fubara et al, 1996). One of the unique features of these receptors is that, in addition to the GABA binding site, the receptor has several allosteric modulatory sites. They are regulated by many positive and negative allosteric modulators including neurotransmitters, neuromodulators and neurohormones (Majewska, 1992; Sapp et al, 1992; Macdonald and Olsen, 1994; Sieghart, 2012; Huidoboro-Toro et al, 1996). Box: 523, Sultan Moulay Slimane University, Béni-Mellal 23000, Morocco Tel: 212-523485112 Fax: 212-523485201
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