Kastin A J, Akerstrom V, Hackler L, Pan W
VA Medical Center and Tulane University School of Medicine, New Orleans, LA 70112-1262, USA.
Horm Metab Res. 2001 Jan;33(1):19-25. doi: 10.1055/s-2001-12621.
Adrenomedullin (ADM) is present both in the periphery and brain. In addition to its peripheral effects, this peptide can exert central effects such as decreasing food ingestion. We used multiple-time regression analysis to determine that labeled ADM can cross from blood to brain with an apparent influx constant (K(I)) of 5.83 +/- 1.44 x 10(-4) ml/g-min, much faster than that of albumin, the vascular control. HPLC showed that almost all of the injected 125I-ADM in the brain was intact, and capillary depletion showed that it could reach the parenchyma of the brain. However, more 125I-ADM was reversibly associated with the brain vasculature than we have seen with any other peptide tested by these methods. After intracerebroventricular injection, 125I-ADM exited the brain with the bulk reabsorption of cerebrospinal fluid at an efflux rate comparable to that of albumin. Although there was no blood-to-brain saturation, in situ brain perfusion of 125I-ADM in blood-free physiological buffer showed self-inhibition by excess unlabeled ADM. This, along with evidence of the lack of protein binding shown by capillary zone electrophoresis, indicated competition for the binding site of ADM at the BBB. The low lipophilicity of ADM determined by the octanol/buffer partition coefficient was also consistent with the prominent reversible association of ADM with the vasculature of the BBB. This suggests a function for ADM at the cerebral blood vessels, such as altering cerebral blood flow and perfusion, without disruption of the BBB.
肾上腺髓质素（ADM）在外周和大脑中均有存在。除了其外周作用外，这种肽还可发挥中枢作用，如减少食物摄入。我们通过多次回归分析确定，标记的ADM能够以5.83±1.44×10⁻⁴ ml/g - min的表观流入常数（K(I)）从血液进入大脑，比血管对照白蛋白快得多。高效液相色谱法显示，注射到大脑中的几乎所有¹²⁵I - ADM都是完整的，毛细血管耗竭显示它可以到达脑实质。然而，与我们用这些方法测试的任何其他肽相比，更多的¹²⁵I - ADM与脑血管系统可逆性结合。脑室内注射后，¹²⁵I - ADM随着脑脊液的大量重吸收以与白蛋白相当的流出速率离开大脑。虽然没有血脑饱和度，但在无血生理缓冲液中对¹²⁵I - ADM进行原位脑灌注显示，过量未标记的ADM会产生自我抑制作用。这一点，连同毛细管区带电泳显示的缺乏蛋白质结合的证据，表明在血脑屏障处存在对ADM结合位点的竞争。由正辛醇/缓冲液分配系数测定的ADM的低亲脂性也与ADM与血脑屏障血管系统的显著可逆性结合一致。这表明ADM在脑血管处具有一种功能，例如改变脑血流量和灌注，而不会破坏血脑屏障。
