Madtes P, Redburn D
J Neurochem. 1985 May;44(5):1520-3. doi: 10.1111/j.1471-4159.1985.tb08790.x.
Nipecotic acid has been demonstrated to block the gamma-aminobutyric acid transport systems. Previous studies have shown that the uptake system is the first transmitter-specific parameter to appear during the development of the rabbit retina. Use of these observations has been made to study the influence on the development of gamma-aminobutyric acid receptors of altering the uptake mechanism by treating newborn pups with nipecotic acid to block GABA transport. The present study of the in vivo metabolism of [3H]nipecotic acid in the CNS measured the changes in the levels of [3H]nipecotic acid in both adult and newborn rabbit retinas after injection of the label into the vitreal chamber. It was found that the effective half-life of [3H]nipecotic acid in the vitreous is about 5 h for adult tissue and 3 h for newborn. In contrast, all retinal fractions retained the label longer, the effective half-lives being about 60 h (adult) and 45 h (newborn). Further, no labeled metabolites of nipecotic acid were detected in either adult or newborn tissue. This study gives evidence that the degradation of nipecotic acid in nervous tissue is minimal and suggests that, although the rate of clearance is faster in neonates, the fate of nipecotic acid in vivo may be similar in both adult and newborn tissues.
已证实尼克酸可阻断γ-氨基丁酸转运系统。先前的研究表明，摄取系统是兔视网膜发育过程中出现的首个递质特异性参数。利用这些观察结果，通过用尼克酸处理新生幼崽以阻断GABA转运来研究改变摄取机制对γ-氨基丁酸受体发育的影响。本研究对中枢神经系统中[3H]尼克酸的体内代谢进行了研究，在将标记物注入玻璃体腔后，测量了成年和新生兔视网膜中[3H]尼克酸水平的变化。结果发现，[3H]尼克酸在玻璃体中的有效半衰期对于成年组织约为5小时，对于新生组织约为3小时。相比之下，所有视网膜组分保留标记物的时间更长，有效半衰期约为60小时（成年）和45小时（新生）。此外，在成年或新生组织中均未检测到尼克酸的标记代谢物。这项研究证明了尼克酸在神经组织中的降解极少，并表明，尽管新生儿的清除率更快，但尼克酸在体内的命运在成年和新生组织中可能相似。
