血管中受体介导的钙离子内流。

Receptor-mediated Ca++ entry in blood vessels.

作者信息

Hester R K

机构信息

Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University, College Station 77843.

出版信息

Microcirc Endothelium Lymphatics. 1989 Feb-Apr;5(1-2):31-53.

PMID:2552272

Abstract

The importance of receptor-mediated Ca++ entry (RMCa++E) relative to Ca++ release and potential-dependent Ca++ entry (PDCa++E) in agonist-induced responses in rabbit aorta and renal artery was quantitatively delineated by utilizing a solution without added Ca++ containing low ethyleneglycol bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) plus D600 to inhibit PDCa++E. Adding an approximate ED80 concentration of norepinephrine (NE; 3 x 10(-7) M), histamine (Hist; 3 x 10(-6) M), or serotonin (5HT; 3 x 10(-6) M) to this solution results in a transient increase in developed force that is attributed to release of a limited cellular pool of Ca++. (NE greater than Hist much greater than 5HT). When the concentrations are approximately equipotent (NE, 3 x 10(-7) M; Hist, 3 x 10(-5) M; 5HT, 10(-5) M) the Ca++ release component increases for Hist and 5HT such that NE = Hist greater than 5HT. Subsequent addition of Ca++ results in an increase in developed force that is sustained and represents RMCa++E. In aorta, RMCa++E can account for 91% of the total NE-induced developed force; for an equipotent concentration of Hist, 71%; and for an equipotent concentration of 5HT, only 37%. This capacity for stimulating RMCa++E is inversely related to the sensitivity of these agonists to the PDCa++E blocker, D600 (5HT much greater than Hist greater than NE). Chronic Mg++ potentiates control responses to NE in normal Ca++, but depresses the sensitivity to Ca++ in the RMCa++E concentration response relationship. The sustained response associated with RMCa++E is only minimally relaxed or inhibited by Mg++ (acute) and is completely inhibited or slowly and completely relaxed by La . In renal artery, a similar approximate ED80 concentration of NE (3 x 10(-6) M) results in a NE-induced transient response attributed to Ca++ release that is 60% less than that seen in aorta, whereas the RMCa++E component in renal artery accounts for 78% of the total response (only 10% less than in aorta). Thus, it appears that there are pharmacologically distinct Ca++ channels in some blood vessels that are differentially activated in a selective and potential-independent manner as a result of specific agonist-receptor interactions.

摘要

通过使用不含添加钙的溶液（含有低浓度乙二醇双（β-氨基乙基醚）-N，N'-四乙酸（EGTA）加D600以抑制电位依赖性钙内流（PDCa++E）），定量描述了受体介导的钙内流（RMCa++E）相对于钙释放和电位依赖性钙内流在兔主动脉和肾动脉激动剂诱导反应中的重要性。向该溶液中添加大约ED80浓度的去甲肾上腺素（NE；3×10⁻⁷M）、组胺（Hist；3×10⁻⁶M）或血清素（5HT；3×10⁻⁶M）会导致所产生的力量短暂增加，这归因于有限的细胞内钙池的释放。（NE＞Hist＞＞5HT）。当浓度大致等效时（NE，3×10⁻⁷M；Hist，3×10⁻⁵M；5HT，10⁻⁵M），Hist和5HT的钙释放成分增加，使得NE = Hist＞5HT。随后添加钙会导致所产生的力量持续增加，这代表RMCa++E。在主动脉中，RMCa++E可占NE诱导的总产生力量的91%；对于等效浓度的Hist，为71%；对于等效浓度的5HT，仅为37%。这种刺激RMCa++E的能力与这些激动剂对PDCa++E阻滞剂D600的敏感性呈负相关（5HT＞＞Hist＞NE）。慢性镁增强了正常钙条件下对NE的对照反应，但降低了RMCa++E浓度反应关系中对钙的敏感性。与RMCa++E相关的持续反应仅被镁（急性）轻微松弛或抑制，而被镧完全抑制或缓慢且完全松弛。在肾动脉中，类似的大约ED80浓度的NE（3×10⁻⁶M）会导致NE诱导的短暂反应，归因于钙释放，该反应比在主动脉中观察到的少60%，而肾动脉中的RMCa++E成分占总反应的78%（仅比主动脉中少10%）。因此，似乎在某些血管中存在药理学上不同的钙通道，由于特定的激动剂-受体相互作用，它们以选择性和电位非依赖性方式被差异激活。