去极化剂对从大鼠切除的颈上神经节和结状神经节中转谷氨酰胺酶活性、钙离子内流及蛋白质合成的影响。

Effects of depolarizing agents on transglutaminase activity, Ca2+ influx, and protein synthesis in superior cervical and nodose ganglia excised from rats.

作者信息

Ando M, Nagata Y

机构信息

Department of Physiology, Fujita Health University School of Medicine, Aichi, Japan.

出版信息

Mol Chem Neuropathol. 1993 May-Jun;19(1-2):121-35. doi: 10.1007/BF03160173.

DOI:10.1007/BF03160173

PMID:8103333

Abstract

Rapid changes in transglutaminase (TG) activity, 45Ca(2+)-influx and [3H]leucine incorporation in superior cervical ganglia (SCG), and nodose ganglia (NG) excised from adult rats were examined following addition of membrane-depolarizing agents veratridine (Ver) or high extracellular [K+]o during aerobic incubation in vitro at 37 degrees C. Addition of KCl (50 mM) stimulated TG activity to a maximal extent (four to six-fold) in SCG and NG after 30 min. Ver (0.2 mM) also increased TG activity in both ganglia after 30 min. Kinetic studies showed that the stimulation of TG activity in both ganglia caused by each depolarization condition was associated with a decrease in Km and an increase in Vmax value. The depolarizing agents Ver and high [K+]o also caused significant increases in 45Ca2+ influx into both ganglia. The Ver-induced increases in TG activity and 45Ca2+ accumulation were antagonized by tetrodotoxin (TTX, 1 microM), a sodium channel blocker. The K(+)-induced increase in TG activity was not blocked by tetraethylammonium (TEA, 20 mM), a potassium channel antagonist, although TEA did block the K(+)-induced increase in 45Ca2+ accumulation. The membrane-perturbing, sialic acid-containing compounds, GM1-ganglioside (GM1, 5 nM) and alpha-sialyl cholesterol (alpha-SC, 20 microM), were moderate inhibitors of the K(+)-induced effects on TG activity and 45Ca2+ accumulation. The sialyl compounds had little effect on Ver-induced accumulation of 45Ca2+ but enhanced the Ver-evoked stimulation in TG activity. These results suggests that the veratridine- and K(+)-induced increases in TG activity occur via modulation of Ca2+ and Na+ channel gating mechanisms that are pharmacologically distinct for each depolarizing agent. The veratridine- and K(+)-induced decrease in [3H]leucine incorporation could be a result of stimulation of TG activity as a consequence of degenerative alterations.

摘要

在37℃有氧体外孵育过程中，添加膜去极化剂藜芦定（Ver）或高细胞外[K⁺]ₒ后，检测成年大鼠切除的颈上神经节（SCG）和结状神经节（NG）中转谷氨酰胺酶（TG）活性、⁴⁵Ca²⁺内流和[³H]亮氨酸掺入的快速变化。添加KCl（50 mM）在30分钟后最大程度地刺激了SCG和NG中的TG活性（四到六倍）。Ver（0.2 mM）在30分钟后也增加了两个神经节中的TG活性。动力学研究表明，每种去极化条件引起的两个神经节中TG活性的刺激与Km降低和Vmax值增加有关。去极化剂Ver和高[K⁺]ₒ也导致两个神经节中⁴⁵Ca²⁺内流显著增加。藜芦定诱导的TG活性增加和⁴⁵Ca²⁺积累被钠通道阻滞剂河豚毒素（TTX，1 μM）拮抗。K⁺诱导的TG活性增加未被钾通道拮抗剂四乙铵（TEA，20 mM）阻断，尽管TEA确实阻断了K⁺诱导的⁴⁵Ca²⁺积累增加。膜扰动性含唾液酸化合物GM1-神经节苷脂（GM1，5 nM）和α-唾液酸胆固醇（α-SC，20 μM）是K⁺诱导的对TG活性和⁴⁵Ca²⁺积累影响的中度抑制剂。唾液酸化合物对藜芦定诱导的⁴⁵Ca²⁺积累影响很小，但增强了藜芦定引起的TG活性刺激。这些结果表明，藜芦定和K⁺诱导的TG活性增加是通过调节Ca²⁺和Na⁺通道门控机制发生的，每种去极化剂的药理学机制不同。藜芦定和K⁺诱导的[³H]亮氨酸掺入减少可能是变性改变导致TG活性刺激的结果。