Pentylenetetrazol誘発痙攣ラットにおける脳内神経ペプチドの関与とTRHおよびceruletideの痙攣に対する影響

INVOLVEMENTS OF NEUROPEPTIDES IN PENTYLENETETRAZOL-INDUCED CONVULSION IN RATS AND EFFECTS OF TRH AND CERULETIDE ON THE CONVULSION

　痙攣の病態生理を解明するため，pentylenetetrazol（PTZ）誘発痙攣ラットを作製し，neuroten—sin（NT）およびsomatostatin（SS）の大脳前頭葉皮質における濃度と，それぞれのレセプターの最大結合部位数（Bmax）および解離定数（Kd）を測定した。さらにthyrotropin-releasing hormone（TRH）およびceruletide（CER）のこれらに対する影響についても検討した。PTZ（50mg／kg）腹腔内投与によりneuro—tensin-like immunoreactivity（NTLI）濃度およびNTレセプターのBmaxは減少したが，somatostatin—like immunoreactivity（SSLI）濃度とSSレセプターには有意の変化はみられなかった。NTを脳室内に前投与するとPTZ痙攣は抑制された。TRHまたはCERを脳室内に前投与するとPTZ痙攣は抑制され，NTレセプターのBmaxはPTZ単独投与群に比べさらに減少した。これらの成績は，NTはPTZ痙攣を抑制すること，TRHおよびCERはNTの放出を促進することにより抗癬攣作用を示すこと，およびPTZ痙攣の発生にSSの関与は少ないことを示唆する。

To study the possible involvements of neuropep-tides in the occurrence of convulsion, pentylene-tetrazol (PTZ) was given to male Wistar rats weighing 250-350 g, and the concentration of neu-rotensin (NT), and the maximal number of bin-ding sites (Bmax) and dissociation constant (Kd) of NT receptor in the frontal cortex were measu-red. The effect of the pretreatment of thyrotropin-releasing hormone (TRH) or ceruletide (CER) onthe convulsion was also studied. NT was extracted from the homogenates of rat frontal cortex by boiling, and measured by radioimmunoassay. Me-mbrane fractions were incubated with increasing concentrations of ¹²⁵I-NT. Nonspecific binding was determined in the presence of unlabeled NT and subtracted from total binding to obtain the spe-cific binding. The Bmax and Kd were calculated by Scatchard analysis. Generalized convulsion ap-peared after intraperitoneal administration of 50 mg/kg PTZ with a latency of 68.2 ±4.4 sec. One hour after the administration, neurotensin-like im-munoreactivity (NTLI) concentration was reduced from 4.7± 0.6 to 2.3± 0.1 ng/g wet wt (p＜0.01) and the Bmax of NT receptor from 17. 2± 2. 8 to 10.8 ± 1.1 fmol/mg protein (p＜0.01). However no significant changes were observed in somatostatin-like immunoreactivity (SSLI) concentration and the Bmax and Kd of SS receptor. These facts indicate that PTZ stimulates the release of NT resulting in down regulation of NT receptor. Pret-reatment with intracerebroventricular (icy) admi-nistration of 30μg/10μg NT 30 min before the 50 mg/kg PTZ administration shorteried the duration of the convulsion from 135.0± 42.8 to 11.5±11 9 sec (p＜0.01). In addition, the icv administration of 60 μg/10 μl TRH or 2 μg/10 μl CER 30 min be-fore the PTZ administration inhibited almost com-pletely the PTZ-induced convulsion, and accelera-ted PTZ-induced reduction in the Bmax of NT rece-ptor without change in the NTLI concentration. The Bmax of SS receptor was decreased in TRH-treated and CER-treated rats, but no significant changes were observed in the SSLI concentration. These results indicate that NT is involved in PTZ-induced convulsion and has an inhibitory effect on the convulsion, and that TRH and CER have an anti-convulsant effect by stimulating the release of NT. SS seems not to involve in acute convulsion induced by PTZ.