Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis.
Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis.
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通过氢氧根离子转运和渗透裂解控制人血小板血清素分泌的证据。
DOI：
10.1073/pnas.74.12.5295
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发表时间：
1977
影响因子：
11.1
通讯作者：
N. Shulman
中科院分区：
文献类型：
--
作者：
H. Pollard;K. Tack;C. Pazoles;C. Creutz;N. Shulman
凝血酶或钙离子载体A23187刺激的人血小板5-羟色胺分泌被阴离子转运阻断剂如4-乙酰氨基-4 '-异硫氰基二苯乙烯-2，2'-二磺酸（SITS）、磷酸吡哆醛、丙磺舒和苏拉明抑制。这些药物先前已被证明可以通过阻断氯化物摄取和随后的渗透溶解来抑制ATP诱发的肾上腺素从离体嗜铬颗粒中的释放。然而，与颗粒释放相反，血小板分泌对氯化物不敏感，而是依赖于OH-。血小板释放被抑制低pH值，和运输阻断药物的抑制是竞争性的，只有相对于OH-。血小板5-羟色胺的释放也受到抑制，通过增加细胞外渗透强度，抑制和外部渗透强度之间的关系是定量类似的嗜铬颗粒的情况下观察到的。我们的结论是，血小板胞吐可能发生时，β-肾上腺素能颗粒紧密并列的质膜，从而暴露颗粒阴离子转运网站的碱性介质。5-羟色胺的分泌可能是颗粒-质膜复合物的OH-转运和渗透溶解的结果，类似于从分离的嗜铬颗粒释放氯依赖性肾上腺素的化学渗透机制。
Serotonin secretion from human platelets, stimulated either by thrombin or the calcium ionophore A23187, was found to be inhibited by anion transport blocking drugs such as 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), pyridoxal phosphate, probenecid, and suramin. These drugs have previously been shown to inhibit ATP-evoked release of epinephrine from isolated chromaffin granules by blocking chloride uptake and subsequent osmotic lysis. However, in contrast to granule release, platelet secretion was insensitive to chloride and, instead, was dependent on OH-. Platelet release was suppressed by low pH, and inhibition by the transport blocking drugs was competitive only with respect to OH-. Serotonin release from platelets was also suppressed by increasing extracellular osmotic strength, and the relationship between suppression and external osmotic strength was quantitatively similar to that observed in the case of chromaffin granules. We conclude that platelet exocytosis could occur when serotonergic granules are closely juxtaposed to the plasma membrane, thus exposing the granule anion transport site to the more alkaline medium. Secretion of serotonin could occur as a consequence of OH- transport and osmotic lysis of the granule-plasma membrane complex, analogous to the chemiosmotic mechanism of chloride-dependent epinephrine release from isolated chromaffin granules.