Mishra R K, Gardner E L, Katzman R, Makman M H
Proc Natl Acad Sci U S A. 1974 Oct;71(10):3883-7. doi: 10.1073/pnas.71.10.3883.
Unilateral radiofrequency lesions or chemical lesions with 6-hydroxydopamine were produced in the substantia nigra of rat brain in order to destroy dopaminergic innervations to caudate nucleus and thereby to produce functional denervation supersensitivity. Both types of lesions resulted in enhanced stimulation of caudate adenylate cyclase (EC 4.6.1.1) activity by dopamine at all dopamine concentrations tested, with more marked enhancement at the lower concentrations. Response to another dopamine agonist, 1-(3,4-dihydroxybenzyl)-4-(20pyrimidinyl) piperazine (S584) was also enhanced. 6-Hydroxydopamine lesions resulted in selective enhancement of the dopamine-stimulated component of adenylate cyclase, whereas radiofrequency lesions resulted also in a marked decrease in basal activity. It is postulated that the basal activity of caudate represents primarily an adenylate cyclase distinct from that stimulated by dopamine and destroyed only by the less selective radiofrequency lesion. The enhancement of dopamine-sensitive adenylate cyclase after lesions serves as indirect evidence for a significant role of this system in the transmitter function of dopamine and indicates, furthermore, that it is directly involved in dopamine receptor supersensitivity in vivo produced by denervation.
为了破坏对尾状核的多巴胺能神经支配从而产生功能性去神经超敏反应，在大鼠脑黑质中制作了单侧射频损伤或用6-羟基多巴胺制作化学损伤。两种损伤类型均导致在所有测试的多巴胺浓度下，多巴胺对尾状核腺苷酸环化酶（EC 4.6.1.1）活性的刺激增强，在较低浓度下增强更为明显。对另一种多巴胺激动剂1-(3,4-二羟基苄基)-4-(2-嘧啶基)哌嗪（S584）的反应也增强。6-羟基多巴胺损伤导致腺苷酸环化酶的多巴胺刺激成分选择性增强，而射频损伤还导致基础活性显著降低。据推测，尾状核的基础活性主要代表一种与多巴胺刺激的腺苷酸环化酶不同的腺苷酸环化酶，且仅被选择性较低的射频损伤破坏。损伤后多巴胺敏感的腺苷酸环化酶增强，这间接证明了该系统在多巴胺递质功能中起重要作用，此外还表明它直接参与了去神经在体内产生的多巴胺受体超敏反应。
