Modulation of central GABAA receptor complex by somatostatin: a pharmacological study.
The goal of the present study was to determine the possible interactions between somatostatin (SST) and gamma-aminobutyric acid (GABA). We thus investigated the SST interaction with [35S]-tertiary butylbicyclophosphorothionate (TBPS) binding sites of the cortical and hippocampal regions of the rat brain. The method used to identify such effects is in vitro quantitative autoradiography. Thus, the binding of the cage convulsant [35S]-TBPS to a picrotoxin-sensitive site in the rat brain was used to investigate the modulatory action of SST on the GABAA receptor complex. The addition of the peptide to the incubation medium results in a dose-dependent inhibition of [35S]-TBPS in cortical and hippocampal structures. Detailed analysis showed a dose-related effect of SST with relative potencies comparable to those observed for 5 alpha 3 alpha P and 5 beta 3 alpha P. In addition, these neurosteroids were able to enhance the efficacy of SST in inhibiting [35S]-TBPS binding. The efficacy of SST in enhancing the inhibitory action of neurosteroids was also evidenced. Furthermore, SST seems to mimic the effects of these neurosteroids as well as GABA and picrotoxin on [35S]-TBPS binding to the rat brain in every context examined. This suggests that somatostatin allosterically modifies [35S]-TBPS binding through a mechanism similar to that of GABA. On the other hand, a possible action of SST via transduction systems on the GABAA receptor complex could also be suggested. These results illustrate the importance of interactions in SST-mediated GABA transmission in these brain regions.
Chigr
F
F
Department of Biology and Biotechnology, Faculty of Sciences and Techniques, Béni-Mellal, Morocco.
Ba M'hamed
S
S
Najimi
M
M
Vincens
M
M
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D015290:Second Messenger Systems; D013004:Somatostatin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018756:GABA Antagonists; D019204:GTP-Binding Proteins; D009419:Nerve Tissue Proteins; D010852:Picrotoxin; D011280:Pregnanolone; D011963:Receptors, GABA-A; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate