Puebla L, Arilla E
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Madrid, Spain.
J Neurosci Res. 1996 Feb 1;43(3):346-54. doi: 10.1002/(SICI)1097-4547(19960201)43:3<346::AID-JNR9>3.0.CO;2-J.
The glycine and somatostatin (SS) neurotransmission systems in the brain have been implicated in the function of sensory, motor, and nociceptive pathways. To investigate a possible relationship between these two components, we studied the influence of glycine on the binding of 125I-Tyr11-SS to its receptors and on SS-like immunoreactivity (SSLI) levels in the rat hippocampus and frontoparietal cortex. An intracerebroventricular (i.c.v.) dose of 16 or 160 nmol of glycine induced an increase in the total number of specific SS receptors in the hippocampus but not in the frontoparietal cortex at 15 min following injection, with no changes in the affinity constant. This effect seems to be mediated by inhibitory strychnine-sensitive glycine receptors since pretreatment with the antagonist strychnine (80 micrograms/100 g body weight, intravenously) abolished this response. No significant changes in SSLI content were detected in either brain region of glycine- and strychnine plus glycine-treated rats as compared to control values. Since SS receptors are coupled via guanine nucleotide-binding G proteins to the adenylyl cyclase (AC) system, we also examined the inhibitory effects of SS and the guanine nucleotide Gpp(NH)p on AC activity in hippocampal membranes of control, glycine- and strychnine plus glycine-treated rats since the increase in SS receptors was observed only in this brain area. No significant differences were observed for the forskolin (FK)-stimulated AC enzyme activities in hippocampal membranes from all the experimental groups studied. In the hippocampus of the glycine- (160 nmol) treated group, however, basal AC activity was significantly lower, and the capacity of SS to inhibit FK-stimulated AC activity was increased as compared to the control group. Pretreatment with strychnine prevented the increase in SS-mediated inhibition of AC activity. The functional activity of the inhibitory guanine nucleotide-binding protein Gi, as determined by the inhibitory effect of the stable GTP analogue Gpp(NH)p on FK-stimulated AC activity, was significantly higher in hippocampal membranes of glycine- (160 nmol) treated rats as compared to controls. This suggests that the increased inhibition of AC activity by SS in the glycine-treated group may be due to the increase in Gi activity and/or the increase in the number of SS receptors observed. Alternatively, the greater Gi activity may be responsible for the increased binding of 125I-Tyr11-SS to its receptors observed after glycine administration. Altogether, these data suggest that the hippocampal somatostatinergic system can be regulated by strychnine-sensitive glycine receptors in the rat.
大脑中的甘氨酸和生长抑素（SS）神经传递系统与感觉、运动和伤害性感受通路的功能有关。为了研究这两个成分之间可能的关系，我们研究了甘氨酸对125I-Tyr11-SS与其受体结合以及对大鼠海马和额顶叶皮质中SS样免疫反应性（SSLI）水平的影响。脑室内（i.c.v.）注射16或160 nmol甘氨酸后15分钟，海马中特异性SS受体总数增加，但额顶叶皮质中未增加，亲和常数无变化。这种效应似乎是由对士的宁敏感的抑制性甘氨酸受体介导的，因为用拮抗剂士的宁（80微克/100克体重，静脉注射）预处理可消除这种反应。与对照值相比，在甘氨酸和士的宁加甘氨酸处理的大鼠的两个脑区中均未检测到SSLI含量的显著变化。由于SS受体通过鸟嘌呤核苷酸结合G蛋白与腺苷酸环化酶（AC）系统偶联，我们还研究了SS和鸟嘌呤核苷酸Gpp(NH)p对对照、甘氨酸和士的宁加甘氨酸处理的大鼠海马膜中AC活性的抑制作用，因为仅在该脑区观察到SS受体增加。在所研究的所有实验组的海马膜中，对于福斯可林（FK）刺激的AC酶活性未观察到显著差异。然而，在甘氨酸（160 nmol）处理组的海马中，基础AC活性显著降低，并且与对照组相比，SS抑制FK刺激的AC活性的能力增加。用士的宁预处理可防止SS介导的AC活性抑制增加。通过稳定的GTP类似物Gpp(NH)p对FK刺激的AC活性的抑制作用测定的抑制性鸟嘌呤核苷酸结合蛋白Gi的功能活性，在甘氨酸（160 nmol）处理的大鼠的海马膜中显著高于对照组。这表明在甘氨酸处理组中SS对AC活性抑制增加可能是由于Gi活性增加和/或观察到的SS受体数量增加。或者，更大的Gi活性可能是甘氨酸给药后观察到的125I-Tyr11-SS与其受体结合增加的原因。总之，这些数据表明大鼠海马中的生长抑素能系统可由对士的宁敏感的甘氨酸受体调节。
