ACTIVATION AND INHIBITION OF CALCIUM-DEPENDENT HISTAMINE-SECRETION BY ATP IONS APPLIED TO RAT MAST-CELLS
ACTIVATION AND INHIBITION OF CALCIUM-DEPENDENT HISTAMINE-SECRETION BY ATP IONS APPLIED TO RAT MAST-CELLS
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DOI：
10.1113/jphysiol.1979.sp013002
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发表时间：
1979-01-01
影响因子：
5.5
通讯作者：
GOMPERTS, BD
中科院分区：
文献类型：
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作者：
COCKCROFT, S;GOMPERTS, BD
在不同浓度的 Mg2+ 和 Ca2+ 存在下，[大鼠]肥大细胞组胺分泌对 ATP 的浓度依赖性证实，ATP 的激动剂形式是不与二价阳离子（即 ATP4-）结合的 ATP 游离形式（ATP（游离））。它在约 1.2 μM 时诱导 50% 活化，在约 2.7 μM 和 50% 时诱导最大分泌约 4.4 μM 的自我抑制在存在高得多浓度的ATP（总）的情况下，使用二价阳离子Mg 2+ 和Ca 2+ 将ATP（游离）缓冲在1-8μM范围内。除了作为 ATP 缓冲剂的作用外，Ca2+ 也是分泌所必需的。当ATP(游离)为1μM时，组胺分泌的时程特征为在分泌开始之前延迟约10分钟。随着 ATP（游离）浓度的增加，延迟变得更短（< 5 分钟，ATP（游离）在 2 μM 时）。当向用低浓度ATP(游离)(<2μM)预处理的细胞添加Ca2+时，分泌立即开始。显然，通常观察到的延迟代表了 Ca2+ 敏感性发展所需的时间（即，可能是 Ca2+ 通道打开所需的时间）。向用较高浓度的ATP(游离)(>2μM)预处理的细胞中后期添加Ca 2+ 导致组胺分泌量与正常情况相比减少。这种减少（随着暴露于 ATP 的时间而增加）和由于较高浓度的 ATP（游离）而导致的自我抑制可能是常见抑制机制的两个方面。这些结果的讨论与以下观察结果相关：用自抑制浓度的 ATP（不含）处理的肥大细胞变得可渗透磷酸化代谢物和核苷酸。
The concentration dependence on ATP of [rat] mast cell histamine secretion in the presence of various concentrations of Mg2+ and Ca2+ confirms that the agonist form of ATP is the free form of ATP (ATP(free)) not bound to divalent cations, i.e., ATP4-.It induces 50% activation at about 1.2 .mu.M, maximal secretion at about 2.7 .mu.M and 50% self-inhibition at about 4.4 .mu.M. The divalent cations Mg2+ and Ca2+ were used to buffer ATP(free) in the range 1-8 .mu.M in the presence of much higher concentrations of ATP(total). In addition to its effect as a buffer for ATP, Ca2+ is required for secretion. With ATP(free) at 1 .mu.M, the time-course of histamine secretion is characterized by a delay of about 10 min before secretion commences. With increasing concentration of ATP(free) the delay becomes shorter (< 5 min with ATP(free) at 2 .mu.M). Secretion commences promptly on addition of Ca2+ to cells pretreated with low concentrations of ATP(free) (< 2 .mu.M). Apparently the delay normally observed represents the time taken for Ca2+ sensitivity to develop (i.e., probably the time taken for Ca2+ channels to open). Late addition of Ca2+ to cells pretreated with higher concentrations of ATP(free) (> 2 .mu.M) results in a reduced amount of histamine secretion compared to that which normally occurs. This reduction (which increases with time of exposure to ATP) and the self-inhibition due to higher concentrations of ATP(free) may be 2 facets of a common inhibitory mechanism. These results are discussed in relation to the observation that mast cells treated with ATP(free) at self-inhibitory concentrations become permeable to phosphorylated metabolites and nucleotides.