Soares-da-Silva P
Department of Pharmacology and Therapeutics Faculty of Medicine, Porto, Portugal.
Pharmacol Res. 1992 Sep;26(2):161-71. doi: 10.1016/s1043-6618(05)80129-x.
The present study has examined the effects of 6-hydroxydopamine (6-OHDA) alone and in combination with pargyline, desipramine and GBR 12909 and denervation as induced by occlusion of the renal artery (RAO) on the endogenous dopamine (DA) and noradrenaline (NA) contents in rat and rabbit renal tissues; the effects of chemical denervation on catecholamine levels in the left ventricle were also studied. In rat and rabbit renal medulla and rat renal cortex, 6-OHDA and pargyline plus 6-OHDA selectively reduced NA (85-92% reduction) without a parallel decrease in DA tissue content (19-27% reduction). This 6-OHDA- and pargyline plus 6-OHDA-insensitive DA pool was found to be resistant to denervation as induced by RAO. The NA-depleting effect of 6-OHDA in these renal areas was found to be prevented by the previous administration of desipramine, but not with that of GBR 12909. In the rabbit renal cortex, 6-OHDA selectively reduced NA (90% reduction) without a parallel depletion of DA (20% reduction); previous treatment with pargyline abolished this selectivity. Again, only desipramine, but not GBR 12909, was found to prevent the NA and DA depleting effect of 6-OHDA in the rabbit renal cortex. Denervation induced by RAO was also found to produce a parallel depletion of DA and NA tissue levels in this renal area. In the left ventricle, 6-OHDA alone or in combination with pargyline produced a parallel depletion of DA and NA tissue levels (79-88% reduction) in both species. These results provide evidence against the presence of independent dopaminergic neurones in rat and rabbit kidney and suggest that in rat and rabbit renal medulla and rat renal cortex most of DA is stored in a non-neuronal compartment; in rabbit renal cortex some of the DA appears to be located in noradrenergic neurones, in a store different from that which contains NA.
本研究考察了单独使用6-羟基多巴胺（6-OHDA）以及联合使用帕吉林、地昔帕明和GBR 12909，还有肾动脉闭塞（RAO）诱导的去神经支配对大鼠和家兔肾组织内源性多巴胺（DA）和去甲肾上腺素（NA）含量的影响；还研究了化学去神经支配对左心室内儿茶酚胺水平的影响。在大鼠和家兔肾髓质以及大鼠肾皮质中，6-OHDA以及帕吉林加6-OHDA选择性地降低了NA（降低85%-92%），而DA组织含量没有相应降低（降低19%-27%）。发现这个对6-OHDA以及帕吉林加6-OHDA不敏感的DA池对RAO诱导的去神经支配具有抗性。发现在这些肾区，预先给予地昔帕明可防止6-OHDA的NA耗竭作用，但GBR 12909则不能。在家兔肾皮质中，6-OHDA选择性地降低了NA（降低90%），而DA没有相应耗竭（降低20%）；预先用帕吉林处理消除了这种选择性。同样，仅发现地昔帕明而非GBR 12909可防止6-OHDA在家兔肾皮质中的NA和DA耗竭作用。还发现RAO诱导的去神经支配在该肾区也使DA和NA组织水平同时耗竭。在左心室中，单独使用6-OHDA或联合使用帕吉林使两个物种的DA和NA组织水平同时耗竭（降低79%-88%）。这些结果提供了证据，反对大鼠和家兔肾脏中存在独立的多巴胺能神经元，并表明在大鼠和家兔肾髓质以及大鼠肾皮质中，大部分DA储存在非神经元区室中；在家兔肾皮质中，一些DA似乎位于去甲肾上腺素能神经元中，储存在与含有NA的储存部位不同的部位。
