実験水頭症ラットにおける脈絡叢125I-endothelin−1特異的結合部位の変化

Alteration of Endothelin-1 Receptor in the Choroid Plexus of Rats with Kaolininduced Experimental Hydrocephalus

　¹²⁵I-endothelin−1（¹²⁵I-ET−1）を用いた定量的receptor autoradiography法で，kaolin誘発実験水頭症ラットの脈絡叢におけるET−1特異的結合部位の変化を観察した。4週齢ラット脈絡叢には高親和性単一（結合親和性常数Ka＝2.6±0.3×10⁹9／M，最大結合能Bmax＝36.2±2.5fmol／mg, n＝5）のET−1特異結合部位が存在した。生後1週齢で25％kaolin懸濁液50μlを大槽内に注入した後3週間経過した実験水頭症群では，Kaは，3.5±0.5×10⁹／M（n＝5）で，有意な変化はなかったが，Bmaxは16.3±0.6fmol／mg（n＝5）と対照群の45％に低下していた。以上の結果は，脈絡叢にET−1受容体が存在し，髄液産生調節に関与していることを示唆している。

Specific binding sites for endothelin-1 (ET-1) in the choroid plexus of rats with kaolin-induced hydrocephalus were analyzed using quantitative receptor autoradiographic technique with ¹²⁵I-ET-1. Unlabeled ET-1 and its natural analog ET-3 inhib-ited the binding of ¹²⁵I-ET-1 to the choroid plexus of control rats with similar high potencies. However, possibly related substances, such as ion channel regulators (ω-conotoxin GVIA, nitrendipine, ver-apamil, diltiazem, α- bungatmtoxin, aconitine, apamin), ouabain and atrial natriuretic peptide did not affect the binding. Scatchard analysis revealed the presence of a single class and high affinity binding sites for ET-1 in the choroid plexus. Thenumber of ¹²⁵I-ET-1 binding sites in the choroid plexus of rats with kaolininduced hydrocephalus was significantly lower, when compared with those in the age-matched control rats ; maximum number of binding sites (Bmax) was 16.3 ± 0.6 and 36.2 ± 2.5 fmol/mg, respectively (p ＜ 0.01, n=5) . There was no signdficant difference in the binding affinities ; affinity constants (Ka) was 2.6 ± 0.3 × 10⁹ M in con-trol rats and 3.5±0.5 ± 10⁹ in hydrocephalic rats (n=5) . These results suggest that ET receptors may play a role in the regulation of cerebrospinal fluid production.