Bay K 8644刺激子宫肌层阶段性收缩的潜在机制。

The mechanisms underlying Bay K 8644-stimulated phasic myometrial contractions.

作者信息

Chien E K, Saunders T, Phillippe M

机构信息

Department of Obstetrics and Gynecology, University of Chicago, Illinois 60637, USA.

出版信息

J Soc Gynecol Investig. 1996 May-Jun;3(3):106-12.

PMID:8796817

Abstract

OBJECTIVE

Phasic myometrial contractions appear to be produced by calcium transients resulting from the activation of the phosphatidylinositol-signaling pathway. Bay K 8644, an L-type calcium channel activator, produces an increase in frequency and intensity of phasic myometrial contractions. These studies were performed to test the hypothesis that Bay K 8644-stimulated contractions were mediated through mechanisms involving phosphoinositide-specific phospholipase C activation and cytosolic calcium oscillation-like mechanisms.

METHODS

In vitro contraction studies and intracellular calcium imaging were performed on longitudinal strips of uterine tissue obtained from mature virgin Sprague-Dawley rats. Isometric contraction data were computer digitized, analyzed for contraction area, and normalized for cross-sectional area. Dose-response studies were performed using previously reported inhibitors of cytosolic calcium oscillation mechanisms. In addition, qualitative inositol-phosphate production studies were performed after prelabeling uterine tissue in vitro with 3H-inositol. Subsequently, the labeled inositol phosphates were separated and recovered using anion exchange chromatography.

RESULTS

Bay K 8644 produced periodic calcium transients or oscillations along with a dose-related increase in contractile activity and a significant increase in inositol-phosphate production. In contrast, neomycin (an inhibitor of phospholipase C), adenine (an inhibitor of calcium-induced calcium release), nifedipine (an L-type calcium channel blocker), and EGTA (a calcium chelator) significantly inhibited Bay K 8644-stimulated contractile activity.

CONCLUSIONS

These results are consistent with the hypothesis that Bay K 8644, through its facilitation of increased intracellular calcium, results in the activation of the phosphatidylinsitol-signaling pathway and cytosolic calcium oscillation-like phenomena, thereby resulting in the generation of phasic myometrial contractions.

摘要

目的

子宫肌层的阶段性收缩似乎是由磷脂酰肌醇信号通路激活所导致的钙瞬变产生的。L型钙通道激活剂Bay K 8644可使子宫肌层阶段性收缩的频率和强度增加。进行这些研究以检验以下假设：Bay K 8644刺激的收缩是通过涉及磷脂酰肌醇特异性磷脂酶C激活和胞质钙振荡样机制的途径介导的。

方法

对从成熟未孕的Sprague-Dawley大鼠获取的子宫组织纵条进行体外收缩研究和细胞内钙成像。等长收缩数据经计算机数字化处理，分析收缩面积，并按横截面积进行标准化。使用先前报道的胞质钙振荡机制抑制剂进行剂量反应研究。此外，在体外用3H-肌醇预标记子宫组织后进行定性肌醇磷酸生成研究。随后，使用阴离子交换色谱法分离并回收标记的肌醇磷酸。