Izquierdo-Claros R M, Boyano-Adánez M C, Larsson C, Gustavsson L, Arilla E
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Brain Res Mol Brain Res. 1997 Jul;47(1-2):99-107. doi: 10.1016/s0169-328x(97)00063-6.
A recent study carried out by our group demonstrated that exogenous dopamine increases the somatostatin (SS) receptor-effector system in the rat striatum. The present study examined the participation of the D1- and D2-dopaminergic systems in the modulation of the rat striatal SS receptor-effector system by use of the D1-receptor agonist and antagonist SKF 38393 and SCH 23390, respectively, and the D2-receptor agonist and antagonist bromocriptine and raclopride, respectively. In view of the rapid onset of dopamine action, the effect of dopaminergic agents on the SS mechanism of action were studied 3 h after their administration. SKF 38393 (4 mg/kg i.p.) or bromocriptine (2 mg/kg i.p.) administered to male Wistar rats increased the number of 125I-Tyr3-SMS receptors in the striatum (52 and 30%, respectively) without changing the affinity constant. The effect of SKF 38393 on 125I-Tyr3-SMS binding was antagonized by the D1-specific antagonist SCH 23390 (0.25 mg/kg i.p.) whereas the effect of bromocriptine was abolished by the D2-specific antagonist raclopride (5 mg/kg i.p.). No change in binding was produced when SKF 38393 or bromocriptine were added directly to the incubation medium. The acute systemic administration of SCH 23390 or raclopride alone had no effect on the binding of 125I-Tyr3-SMS to its receptors. The increase of the number of 125I-Tyr3-SMS receptor induced by SKF 38393 or bromocriptine was accompanied by an increase in the capacity of SMS 201-995 to inhibit basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity when compared to the control groups. In addition, the effect of SMS 201-995 on the mass accumulation of inositol 1,4,5-trisphosphate (IP3) was investigated. SKF 38393 as well as bromocriptine increased the capacity of SMS 201-995 to accumulate IP3 in the rat striatum although this effect was only statistically significant in the case of SKF 38393. These results suggest that the activation of D1 and D2 receptors increases the activity of the SS receptor-effector system, the effect being greater in the case of D1 receptors. These findings are consistent with a functional interaction between dopamine and SS in the rat striatum.
我们小组最近进行的一项研究表明，外源性多巴胺可增加大鼠纹状体中生长抑素（SS）受体 - 效应系统。本研究通过分别使用D1受体激动剂和拮抗剂SKF 38393和SCH 23390，以及D2受体激动剂和拮抗剂溴隐亭和雷氯必利，研究了D1和D2多巴胺能系统在调节大鼠纹状体SS受体 - 效应系统中的作用。鉴于多巴胺作用起效迅速，在给药3小时后研究了多巴胺能药物对SS作用机制的影响。给雄性Wistar大鼠腹腔注射SKF 38393（4mg/kg）或溴隐亭（2mg/kg）可增加纹状体中125I - Tyr3 - SMS受体的数量（分别增加52%和30%），而不改变亲和力常数。D1特异性拮抗剂SCH 23390（0.25mg/kg腹腔注射）可拮抗SKF 38393对125I - Tyr3 - SMS结合的作用，而D2特异性拮抗剂雷氯必利（5mg/kg腹腔注射）可消除溴隐亭的作用。当将SKF 38393或溴隐亭直接添加到孵育介质中时，结合没有变化。单独急性全身给予SCH 23390或雷氯必利对125I - Tyr3 - SMS与其受体的结合没有影响。与对照组相比，SKF 38393或溴隐亭诱导的125I - Tyr3 - SMS受体数量增加伴随着SMS 201 - 995抑制基础和福斯高林（FK）刺激的腺苷酸环化酶（AC）活性能力的增加。此外，还研究了SMS 201 - 995对肌醇1,4,5 - 三磷酸（IP3）大量积累的影响。SKF 38393以及溴隐亭增加了SMS 201 - 995在大鼠纹状体中积累IP3的能力，尽管这种作用仅在SKF 38393的情况下具有统计学意义。这些结果表明，D1和D2受体的激活增加了SS受体 - 效应系统的活性，在D1受体的情况下作用更大。这些发现与大鼠纹状体中多巴胺和SS之间的功能相互作用一致。
