Boyano-Adánez M C, Bodega G, Martín-Espinosa A, Arilla E
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Madrid, Spain.
Brain Res. 1995 Aug 7;688(1-2):1-7. doi: 10.1016/0006-8993(95)00377-3.
Previous results from our group showed that hyperammonemia decreases the number of somatostatin (SS) receptors and that benzodiazepine receptors might regulate the number of SS receptors in rat brain. These findings together with the supersensitivity of benzodiazepine receptors in the hyperammonemic rat brain suggest that benzodiazepine receptors might mediate the effect of hyperammonemia on SS receptors. To assess this hypothesis we tested whether 2-phenylpyrazolo[3,4-c]-quinolin-3(5H)-one (CGS 8216), a benzodiazepine antagonist, prevented the effect of ammonium acetate on rat brain SS receptors. Administration of ammonium acetate (5 mmol/kg, i.p.) for 7 days did not affect the levels of somatostatin-like immunoreactivity but decreased the number of SS receptors in synaptosomes from the frontoparietal cortex and hippocampus without affecting their apparent affinity. This decrease could be blocked by the concomitant administration of CGS 8216 (10 mg/kg, i.p.). The benzodiazepine antagonist alone had no observable effect on the somatostatinergic system. These results suggested that the effect of hyperammonemia on SS receptors could be mediated, at least in part, through the benzodiazepine receptors.
我们研究小组之前的结果表明，高氨血症会减少生长抑素（SS）受体的数量，并且苯二氮䓬受体可能会调节大鼠脑中SS受体的数量。这些发现，再加上高氨血症大鼠脑中苯二氮䓬受体的超敏反应，表明苯二氮䓬受体可能介导高氨血症对SS受体的影响。为了评估这一假设，我们测试了苯二氮䓬拮抗剂2-苯基吡唑并[3,4-c]-喹啉-3(5H)-酮（CGS 8216）是否能阻止醋酸铵对大鼠脑SS受体的作用。腹腔注射醋酸铵（5 mmol/kg），持续7天，对生长抑素样免疫反应水平没有影响，但减少了额叶顶叶皮质和海马突触体中SS受体的数量，而不影响其表观亲和力。同时注射CGS 8216（10 mg/kg，腹腔注射）可阻断这种减少。单独使用苯二氮䓬拮抗剂对生长抑素能系统没有明显影响。这些结果表明，高氨血症对SS受体的影响至少部分可以通过苯二氮䓬受体介导。
