Zawilska J B, Derbiszewska T, Sek B, Nowak J Z
Department of Biogenic Amines, Polish Academy of Sciences, Lódź, Poland.
Neurochem Int. 1995 Dec;27(6):535-43. doi: 10.1016/0197-0186(95)00033-5.
Stimulation of a D4-like dopamine (DA) receptors inhibits a cAMP-dependent increase in serotonin N-acetyltransferase activity and melatonin biosynthesis in the chick retina. In order to gain more insight into the molecular mechanisms underlying this suppressive action of DA, the effects of selective stimulation of the D2-family of DA receptors (including the D4-subtype) on cAMP formation were examined in chick retina using two experimental approaches: measurements of adenylyl cyclase activity in retinal homogenates, and cAMP accumulation in eye cup preparation prelabeled with [3H]adenine. The DA-sensitive adenylyl cyclase system is well expressed in chick retina. DA increased both basal and forskolin-stimulated adenylyl cyclase activity. This effect of DA was antagonized by SCH 23390 (a blocker of D1-family of DA receptors) and not affected by sulpiride (a D20-family blocker). Incubation of retinal homogenates with quinpirole (a predominant agonist of D3/D4 DA receptor subtypes) did not produce any major changes in adenylyl cyclase activity. On the other hand, activation of D4-like DA receptor subtype by quinpirole decreased forskolin-stimulated cAMP formation in intact chick retina maintained in "eye-cup" preparations. It is suggested that D4-like DA receptors regulating melatonin biosynthesis in chick retina may be indirectly linked to the cAMP generating system.
刺激D4样多巴胺（DA）受体可抑制鸡视网膜中血清素N - 乙酰转移酶活性和褪黑素生物合成的cAMP依赖性增加。为了更深入了解DA这种抑制作用的分子机制，我们采用两种实验方法在鸡视网膜中研究了选择性刺激DA受体的D2家族（包括D4亚型）对cAMP形成的影响：测量视网膜匀浆中的腺苷酸环化酶活性，以及在预先用[3H]腺嘌呤标记的眼杯制剂中测量cAMP积累。DA敏感的腺苷酸环化酶系统在鸡视网膜中表达良好。DA增加了基础和福斯高林刺激的腺苷酸环化酶活性。DA的这种作用被SCH 23390（一种D1家族DA受体阻滞剂）拮抗，而不受舒必利（一种D20家族阻滞剂）影响。用喹吡罗（一种D3/D4 DA受体亚型的主要激动剂）孵育视网膜匀浆不会使腺苷酸环化酶活性产生任何重大变化。另一方面，在“眼杯”制剂中保持的完整鸡视网膜中，喹吡罗激活D4样DA受体亚型会降低福斯高林刺激的cAMP形成。提示调节鸡视网膜中褪黑素生物合成的D4样DA受体可能与cAMP生成系统间接相关。
