猫灌注肾上腺中儿茶酚胺释放与钠泵抑制之间的相关性。
Correlation between catecholamine release and sodium pump inhibition in the perfused adrenal gland of the cat.
作者信息
Garcia A G, Garcia-Lopez E, Montiel C, Nicolas G P, Sanchez-Garcia P
出版信息
Br J Pharmacol. 1981 Nov;74(3):665-72. doi: 10.1111/j.1476-5381.1981.tb10477.x.
1 Ca(2+) reintroduction to retrogradely perfused and ouabain (10(-4) M)-treated cat adrenal glands caused a catecholamine secretory response which was greater the longer the time of exposure to the cardiac glycoside. Such a response was proportional to the external Na(+) concentration Na(+).2 A qualitatively similar, yet smaller response was observed when glands were perfused with Krebs solution lacking K(+) ions; thus, K(+) deprivation mimicked the secretory effects of ouabain. Catecholamine secretion evoked by Ca(2+) reintroduction in K(+)-free solution (0-K(+)) was also proportional to Na(+) and greater the longer the time of exposure of the gland to 0-K(+) solution.3 The ionophore X537A also mimicked the ouabain effects, since Ca(2+) reintroduction to glands treated with this agent (25 muM) caused a sharp secretory response. When added together with X537A, ouabain (10(-4) M) did not modify the response to the ionophore.4 N-ethylmaleimide (NEM), another Na(+), K(+)-ATPase inhibitor, did not evoke the release of catecholamines; on the contrary, NEM (10(-4) M) inhibited the catecholamine secretory response to high K(+), acetylcholine, Ca(2+) reintroduction and ouabain.5 Ouabain (10(-4) M) inhibited the uptake of (86)Rb into adreno-medullary tissue by 60%. Maximal inhibition had already occurred 2 min after adding the drug, indicating a lack of temporal correlation between ATPase inhibition and the ouabain secretory response, which took longer (about 30-40 min) to reach its peak. NEM (10(-4) M) blocked (86)Rb uptake in a similar manner.6 The results are further evidence in favour of the presence of a Na(+)-Ca(2+) exchange system in the chromaffin cell membrane, probably involved in the control of Ca(2+) and in the modulation of catecholamine secretion. This system is activated by increasing Na(+), either directly (ionophore X537A, increased Na(+)) or indirectly (Na(+) pump inhibition). However, the simple inhibition of Na(+) pumping does not always lead to a catecholamine secretory response; such is the case for NEM.
向经哇巴因（10⁻⁴ M）处理后逆行灌注的猫肾上腺重新引入Ca²⁺会引发儿茶酚胺分泌反应，暴露于强心苷的时间越长，该反应就越大。这种反应与细胞外Na⁺浓度[Na⁺]ₒ成正比。
当用不含K⁺离子的 Krebs 溶液灌注腺体时，观察到定性上相似但较小的反应；因此，K⁺缺乏模拟了哇巴因的分泌作用。在无K⁺溶液（0 - K⁺）中重新引入Ca²⁺所诱发的儿茶酚胺分泌也与[Na⁺]ₒ成正比，且腺体暴露于0 - K⁺溶液的时间越长，反应越大。
离子载体X537A也模拟了哇巴因的作用，因为向用该试剂（25 μM）处理过的腺体重新引入Ca²⁺会引发急剧的分泌反应。当与X537A一起添加时，哇巴因（10⁻⁴ M）不会改变对离子载体的反应。
另一种Na⁺,K⁺ - ATP酶抑制剂N - 乙基马来酰亚胺（NEM）不会引发儿茶酚胺释放；相反，NEM（10⁻⁴ M）抑制了对高[K⁺]ₒ、乙酰胆碱、重新引入Ca²⁺和哇巴因的儿茶酚胺分泌反应。
哇巴因（10⁻⁴ M）使肾上腺髓质组织对⁸⁶Rb的摄取减少60%。添加药物后2分钟内就已出现最大抑制，这表明ATP酶抑制与哇巴因分泌反应之间缺乏时间相关性，后者达到峰值所需时间更长（约30 - 40分钟）。NEM（10⁻⁴ M）以类似方式阻断⁸⁶Rb摄取。
这些结果进一步证明嗜铬细胞膜中存在Na⁺ - Ca²⁺交换系统，可能参与[Ca²⁺]i的控制和儿茶酚胺分泌的调节。该系统可通过直接（离子载体X537A、增加[Na⁺]ₒ）或间接（抑制Na⁺泵）增加[Na⁺]i来激活。然而，单纯抑制Na⁺泵并不总是导致儿茶酚胺分泌反应；NEM的情况就是如此。
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