Sweep C G, Boomkamp M D, Barna I, Logtenberg A W, Wiegant V M
Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Acta Endocrinol (Copenh). 1990 Feb;122(2):191-200. doi: 10.1530/acta.0.1220191.
The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of beta-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4-9) (1.44 fmol), N alpha-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of beta-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1-9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied beta-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel beta-endorphin-(1-31), the beta-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of beta-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lives of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol beta-endorphin-(1-31)) significantly enhanced the disappearance of beta-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of beta-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain.
在大鼠中研究了脑室内（侧脑室）注射精氨酸8-加压素（AVP）对从大池获得的脑脊液中β-内啡肽免疫反应性浓度的影响。注射0.9 fmol AVP后5分钟观察到下降。用0.09或9 fmol对大鼠进行脑室内处理5分钟后未发现统计学上的显著变化。0.9 fmol AVP引起的下降持续时间较短，在处理后5分钟出现，但10分钟和20分钟时未出现。脑室内注射去甘氨酰胺9-AVP（0.97 fmol）、[pGlu4，Cyt6]-AVP-（4-9）（1.44 fmol）、Nα-乙酰-AVP（0.88 fmol）、赖氨酸8-加压素（0.94 fmol）和催产素（1 fmol）5分钟后不影响脑脊液中β-内啡肽免疫反应性水平。这表明完整的AVP-（1-9）分子对此效应是必需的。用加压素V1受体拮抗剂d（CH2）5Tyr（Me）AVP（8.63 fmol）对大鼠进行脑室内预处理可完全阻断AVP（0.9 fmol）的作用。为了进一步研究潜在机制，测定了AVP对外源性应用的β-内啡肽从脑脊液中消失的影响。脑室内注射1.46 pmol骆驼β-内啡肽-（1-31）后，大池脑脊液中β-内啡肽免疫反应性水平迅速升高，并在10分钟时达到峰值。然后，脑脊液中β-内啡肽免疫反应性的消失呈双相模式，初始阶段和终末阶段的计算半衰期分别为28分钟和131分钟。在任一阶段（脑室内注射1.46 pmolβ-内啡肽-（1-31）后10、30、55分钟）用AVP（0.9 fmol；脑室内注射）处理大鼠，均显著增强了脑脊液中β-内啡肽免疫反应性的消失。数据表明，加压素通过调节大脑中V1受体的清除机制，在脑脊液中β-内啡肽水平的调节中发挥作用。
