Department of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Peptides. 2011 Jul;32(7):1422-30. doi: 10.1016/j.peptides.2011.06.002. Epub 2011 Jun 13.
Caveolae may act as mechanosensors and function as binding sites for calcium ions. The intracaveolar localization of atrial natriuretic peptide (ANP) derived from the direct interaction of atrial granules with caveolae has been demonstrated. The aim of this study was to define the effect of caveolae on ANP secretion induced by stretch and angiotensin II. The isolated perfused beating atria from Sprague-Dawley rats were used. To disrupt caveolae, 10mM methyl-β-cyclodextrin (MbCD) was applied for 1h and the number of caveoli were markedly decreased. MbCD increased basal ANP secretion and atrial diastolic pressure. The molecular profile of ANP in perfusate from control atria showed mainly one major peak corresponded to synthetic ANP whereas that from MbCD-treated atria showed two major immunoreactive peaks corresponded to synthetic rat ANP and proANP. High atrial stretch induced by elevating the height of outflow catheter from 5 cm H₂O to 7.5 cm H₂O increased atrial contractility and ANP secretion. The response of ANP secretion to high stretch was attenuated in MbCD-pretreated atria. Pretreatment with MbCD abolished angiotensin II-induced suppression and losartan-induced stimulation of ANP secretion. However, the effect of angiotenisin (1-7) on ANP secretion was not altered by MbCD treatment. The expression of angiotensin II type 1 receptor protein was reduced by MbCD treatment. These data suggest that caveolae are essential for angiotensin II type 1 receptor-mediated ANP secretion and relate to the processing of proANP.
小窝可能作为机械感受器，并作为钙离子的结合位点发挥作用。已经证明，心房利钠肽（ANP）来源于心房颗粒与小窝的直接相互作用，其在小窝内的定位。本研究的目的是确定小窝对伸展和血管紧张素 II 诱导的 ANP 分泌的影响。使用来自 Sprague-Dawley 大鼠的分离灌流跳动心房。为了破坏小窝，应用 10mM 甲基-β-环糊精（MbCD）1h，小窝的数量明显减少。MbCD 增加了基础 ANP 分泌和心房舒张压。来自对照心房灌流液的 ANP 的分子谱显示主要一个主要峰对应于合成的 ANP，而来自 MbCD 处理的心房的 ANP 显示两个主要免疫反应性峰对应于合成的大鼠 ANP 和 proANP。通过将流出导管的高度从 5cmH₂O 升高到 7.5cmH₂O 来升高心房，可引起心房伸展，增加心房收缩力和 ANP 分泌。MbCD 预处理心房中 ANP 分泌对高伸展的反应减弱。MbCD 预处理消除了血管紧张素 II 诱导的 ANP 分泌抑制和 losartan 诱导的刺激。然而，MbCD 处理并未改变血管紧张素（1-7）对 ANP 分泌的作用。MbCD 处理降低了血管紧张素 II 型 1 受体蛋白的表达。这些数据表明，小窝是血管紧张素 II 型 1 受体介导的 ANP 分泌所必需的，并且与 proANP 的处理有关。
