Modulation of central GABA(A) receptor complex by somatostatin: a pharmacological study

The goal of the present study was to determine the possible interactions be tween somatostatin (SST) and gamma-aminobutyric acid (GABA). We thus invest igated the SST interaction with [S-35]-tertiary butylbicyclophosphorothiona te (TBPS) binding sites of the cortical and hippocampal regions of the rat brain. The method used to identify such effects is in vitro quantitative au toradiography. Thus, the binding of the cage convulsant [S-35]-TBPS to a pi crotoxin-sensitive site in the rat brain was used to investigate the modula tory action of SST on the GABA(A) receptor complex. The addition of the pep tide to the incubation medium results in a dose-dependent inhibition of [35 S]-TBPS in cortical and hippocampal structures. Detailed analysis showed a dose-related effect of SST with relative potencies comparable to those obse rved for 5 alpha 3 alpha P and 5 beta 3 alpha P. In addition, these neurost eroids were able to enhance the efficacy of SST in inhibiting [S-35]TBPS bi nding. The efficacy of SST in enhancing the inhibitory action of neurostero ids was also evidenced. Furthermore, SST seems to mimic the effects of thes e neurosteroids as well as GABA and picrotoxin on [S-35]-TBPS binding to th e rat brain in every context examined. This suggests that somatostatin allo sterically modifies [S-35]-TBPS binding through a mechanism similar to that of GABA. On the other hand, a possible action of SST via transduction syst ems on the GABA(A) receptor complex could also be suggested. These results illustrate the importance of interactions in SST-mediated GABA transmission in these brain regions.