{"title":"Ca(2+)通道激动剂Bay k8644对人胎盘静脉收缩反应的影响","authors":"M T Barrús, J Reviriego, J Marín","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>1. The aim of the present study was to analyse, in segments of human placental veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 microM) and Ca2+ channel antagonists nifedipine (0.1 microM) and diltiazem (1 microM) on vascular contractility and 45Ca2+ uptake. 2. The Ca2+ channel agonist Bay K 8644 (0.1 microM) caused small concentration dependent contractions that were increased by a moderate membrane depolarization with 7.5 mM K+. This increase was reversed by nifedipine and diltiazem. Ca2+ addition to segments previously depolarized with 75 mM K+ and exposed to a Ca(2+)-free medium caused contractile responses that were increased by 0.1 microM Bay K 8644; such an increase was blocked by 0.1 microM nifedipine and 1 microM diltiazem. 3. K+ and 5-HT induced concentration dependent contractile responses which were increased by Bay K 8644 (0.1 microM). Both 0.1 microM nifedipine and 1 microM diltiazem inhibited the increasing effect of Bay K 8644. Bay K 8644 (30 nM and 0.1 microM) caused an enhancement in 45Ca2+ accumulation over the basal value, that was increased by membrane depolarization with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 microM). K+ (15 and 30, but not 7.5 mM) and 5-HT (1 microM) induced 45Ca2+ uptake over the basal level that was increased by Bay K 8644 (0.1 microM). Such an increase was antagonized by nifedipine (0.1 microM). 4. These data indicate that: (1) a small depolarization with K+ is needed for Bay K 8644 to be able to produce consistent contractile responses, suggesting that voltage gated Ca2+ channels (VGCCs) are not activated in a basal situation in placental veins; (2) the increase of 5-HT contraction by Bay K 8644 may be produced by either the capability of this amine to depolarize the membrane of smooth muscle cells and subsequent facilitation of Ca2+ influx through VGCCs or direct activation by Bay K 8644 of receptor (5-HT) operated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644 appears to be due to a Ca2+ entry activation through VGCCs.</p>","PeriodicalId":15103,"journal":{"name":"Journal of autonomic pharmacology","volume":"16 3","pages":"161-7"},"PeriodicalIF":0.0000,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of the Ca(2+)-channel agonist Bay K 8644 on the contractile responses in human placental veins.\",\"authors\":\"M T Barrús, J Reviriego, J Marín\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>1. The aim of the present study was to analyse, in segments of human placental veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 microM) and Ca2+ channel antagonists nifedipine (0.1 microM) and diltiazem (1 microM) on vascular contractility and 45Ca2+ uptake. 2. The Ca2+ channel agonist Bay K 8644 (0.1 microM) caused small concentration dependent contractions that were increased by a moderate membrane depolarization with 7.5 mM K+. This increase was reversed by nifedipine and diltiazem. Ca2+ addition to segments previously depolarized with 75 mM K+ and exposed to a Ca(2+)-free medium caused contractile responses that were increased by 0.1 microM Bay K 8644; such an increase was blocked by 0.1 microM nifedipine and 1 microM diltiazem. 3. K+ and 5-HT induced concentration dependent contractile responses which were increased by Bay K 8644 (0.1 microM). Both 0.1 microM nifedipine and 1 microM diltiazem inhibited the increasing effect of Bay K 8644. Bay K 8644 (30 nM and 0.1 microM) caused an enhancement in 45Ca2+ accumulation over the basal value, that was increased by membrane depolarization with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 microM). K+ (15 and 30, but not 7.5 mM) and 5-HT (1 microM) induced 45Ca2+ uptake over the basal level that was increased by Bay K 8644 (0.1 microM). Such an increase was antagonized by nifedipine (0.1 microM). 4. These data indicate that: (1) a small depolarization with K+ is needed for Bay K 8644 to be able to produce consistent contractile responses, suggesting that voltage gated Ca2+ channels (VGCCs) are not activated in a basal situation in placental veins; (2) the increase of 5-HT contraction by Bay K 8644 may be produced by either the capability of this amine to depolarize the membrane of smooth muscle cells and subsequent facilitation of Ca2+ influx through VGCCs or direct activation by Bay K 8644 of receptor (5-HT) operated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644 appears to be due to a Ca2+ entry activation through VGCCs.</p>\",\"PeriodicalId\":15103,\"journal\":{\"name\":\"Journal of autonomic pharmacology\",\"volume\":\"16 3\",\"pages\":\"161-7\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1996-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of autonomic pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of autonomic pharmacology","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
1. 本研究的目的是分析,在人类胎盘静脉段,Ca2+通道激动剂Bay K 8644(0.1微米)和Ca2+通道拮抗剂硝苯地平(0.1微米)和地尔硫卓(1微米)对血管收缩性和45Ca2+吸收的影响。2. Ca2+通道激动剂Bay K 8644(0.1微米)引起小的浓度依赖性收缩,并通过7.5毫米K+适度的膜去极化而增加。硝苯地平和地尔硫卓逆转了这种增加。Ca2+加入到先前用75 mM K+去极化的片段中,暴露于无Ca(2+)的介质中,导致收缩反应增加0.1 microM Bay K 8644;0.1 μ m硝苯地平和1 μ m地尔硫卓阻断了这种增加。3.K+和5-HT诱导了浓度依赖性的收缩反应,Bay K 8644 (0.1 μ m)增强了收缩反应。0.1 μ m硝苯地平和1 μ m地尔硫卓均抑制了Bay k8644的增殖作用。Bay K 8644 (30 nM和0.1 microM)使45Ca2+的积累高于基础值,K+(7.5、15和30 nM)使45Ca2+的积累增加,硝苯地平(0.1 microM)抑制45Ca2+的积累。K+(15和30,但不是7.5 mM)和5-HT(1微米)诱导45Ca2+摄取超过基础水平,Bay K 8644(0.1微米)增加。硝苯地平(0.1微米)可拮抗这种增加。4. 这些数据表明:(1)Bay K 8644需要少量的K+去极化才能产生一致的收缩反应,这表明在胎盘静脉的基础情况下,电压门控Ca2+通道(VGCCs)没有被激活;(2) Bay K 8644增加5-HT收缩可能是由于该胺能够使平滑肌细胞膜去极化并随后通过VGCCs促进Ca2+内流,或者Bay K 8644直接激活受体(5-HT)操作的Ca2+通道(ROCs)。(3)Bay K 8644增加的效果似乎是由于Ca2+通过VGCCs进入激活。
Effect of the Ca(2+)-channel agonist Bay K 8644 on the contractile responses in human placental veins.
1. The aim of the present study was to analyse, in segments of human placental veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 microM) and Ca2+ channel antagonists nifedipine (0.1 microM) and diltiazem (1 microM) on vascular contractility and 45Ca2+ uptake. 2. The Ca2+ channel agonist Bay K 8644 (0.1 microM) caused small concentration dependent contractions that were increased by a moderate membrane depolarization with 7.5 mM K+. This increase was reversed by nifedipine and diltiazem. Ca2+ addition to segments previously depolarized with 75 mM K+ and exposed to a Ca(2+)-free medium caused contractile responses that were increased by 0.1 microM Bay K 8644; such an increase was blocked by 0.1 microM nifedipine and 1 microM diltiazem. 3. K+ and 5-HT induced concentration dependent contractile responses which were increased by Bay K 8644 (0.1 microM). Both 0.1 microM nifedipine and 1 microM diltiazem inhibited the increasing effect of Bay K 8644. Bay K 8644 (30 nM and 0.1 microM) caused an enhancement in 45Ca2+ accumulation over the basal value, that was increased by membrane depolarization with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 microM). K+ (15 and 30, but not 7.5 mM) and 5-HT (1 microM) induced 45Ca2+ uptake over the basal level that was increased by Bay K 8644 (0.1 microM). Such an increase was antagonized by nifedipine (0.1 microM). 4. These data indicate that: (1) a small depolarization with K+ is needed for Bay K 8644 to be able to produce consistent contractile responses, suggesting that voltage gated Ca2+ channels (VGCCs) are not activated in a basal situation in placental veins; (2) the increase of 5-HT contraction by Bay K 8644 may be produced by either the capability of this amine to depolarize the membrane of smooth muscle cells and subsequent facilitation of Ca2+ influx through VGCCs or direct activation by Bay K 8644 of receptor (5-HT) operated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644 appears to be due to a Ca2+ entry activation through VGCCs.