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The Pharmacological study on the species differences in the responses of smooth muscle to vasodilator drugs

平滑肌对扩血管药物反应的种属差异的药理学研究

基本信息

批准号：
60480085
负责人：
KARAKI Hideaki
金额：
$ 4.42万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

Species and regional differences in the response of isolated smooth muscle to vasodilator drugs were examined using isolated rabbit and rat aortae and guinea pig taenia coli. Comparing the contractions induced by either high concentrations of K and receptor agonists in these smooth muscle, it was found that (1) addition of receptor agonists to the muscle maximally activated by high K elicited additional contraction, and (2) in the muscle treated with high K, but not by receptor agonists, Sr and Ba ions entered the cell to elicit contraction. These results suggest the existence of two distinctive Ca channels in these smooth muscles, voltage-dependent channel (VDC) which is activated by membrane depolarization and passes Ca, Sr and Ba, and receptor-linked channel (RLC) which is activated by receptor agonists and passes only Ca. In the next series of experiments, effects of vasodilators on these Ca channels were examined. Ca channel blockers and facilitators relatively selectively modulated the VDC in rabbit aorta although both of the channels were relatively nonselectively affected in rat aorta and guinea pig taenia. In contrast to this, nitro-compounds relatively selectively inhibited RLC in rabbit aorta, relatively nonselectively in rat aorta and had showed little effect in the taenia. The aorta isolated from newborn rabbit showed similar characteristics as those in rat aorta and gradually changed with age. These results suggest the existence of species, regional and age-related changes in the sensitivity of Ca channels to vasodilators in smooth muscle.

用兔、大鼠离体主动脉和豚鼠结肠带研究了血管扩张剂药物对离体主动脉和豚鼠结肠带的反应的种类和区域差异。比较高浓度钾和受体激动剂引起的收缩，发现(1)在高钾激活最大的肌肉中加入受体激动剂可引起额外的收缩；(2)在高钾处理的肌肉中，锶和钡离子进入细胞引起收缩。这些结果表明，在这些平滑肌中存在两种不同的钙通道，电压依赖性通道(VDC)和受体连接通道(RLC)，电压依赖性通道(VDC)由膜去极化激活，通过钙、锶和钙，受体连接通道(RLC)由受体激动剂激活，仅通过钙。在接下来的一系列实验中，研究了血管扩张剂对这些钙通道的影响。钙通道阻滞剂和促进剂对兔主动脉的VDC具有相对选择性的调节作用，而在大鼠和豚鼠的主动脉中，这两种通道都相对非选择性地受到影响。与此相反，硝基化合物相对选择性地抑制兔主动脉的RLC，对大鼠的主动脉相对非选择性地抑制RLC，而对牛带绦虫的抑制作用不明显。分离的新生兔主动脉具有与大鼠相似的特征，并随年龄的增长而逐渐改变。这些结果提示，在血管扩张剂的敏感性上，存在种属、区域性和年龄相关的变化。