RELATIONSHIP BETWEEN CALCIUM EXCHANGE AND ENZYME SECRETION IN ISOLATED RAT PANCREAS
RELATIONSHIP BETWEEN CALCIUM EXCHANGE AND ENZYME SECRETION IN ISOLATED RAT PANCREAS
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DOI：
10.1113/jphysiol.1973.sp010379
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发表时间：
1973-01-01
影响因子：
5.5
通讯作者：
CLAUSEN, T
中科院分区：
文献类型：
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作者：
CASE, RM;CLAUSEN, T
1.本研究通过幼鼠离体钩状胰腺45 Ca交换与淀粉酶分泌的相关性，探讨细胞外和细胞内Ca 2+在胰腺酶分泌中的作用. 45 Ca从预载腺体流出的速率系数持续下降（表明45 Ca被保留在几个不同的池中），可能反映了细胞质游离45 Ca浓度的变化，这是由45 Ca从细胞内细胞器释放到细胞质的速率决定的. 45 Ca释放速率系数不受细胞外Ca 2+或Mg 2+浓度的影响。4.胆囊收缩素-胰酶素（CCK-PZ）和乙酰胆碱以剂量依赖的方式加速45 Ca和淀粉酶的释放，即使细胞外Ca 2+降低到0·1 mM，但不影响组织摄取45 Ca的初始速率.在无Ca 2+培养基（含0·5 mM-EGTA）中，基础淀粉酶分泌缓慢下降，刺激分泌几乎消失，但45 Ca的加速释放被抑制.这些观察结果表明，胰腺酶分泌的自然刺激通过一个过程改变细胞中45 Ca的分布，该过程不依赖于细胞外Ca 2+，并且与淀粉酶分泌有关，前提是质膜尚未耗尽Ca 2+。促胰液素、胰高血糖素和胰岛素对45 Ca释放无影响。促胰液素轻微增加淀粉酶分泌，但这可能是一种洗脱效应。Li+替代细胞外Na+可增加45 Ca和淀粉酶的释放，但仅在细胞外Ca ~（2+）存在的情况下。Li+-取代也增加了45 Ca摄取。因此，在特殊条件下，当细胞外来源的Ca 2+增加时，分泌可能会受到刺激。高渗透压（已知增加肌肉中45 Ca的释放）也加速45 Ca的释放和淀粉酶的分泌。2，4-二硝基苯酚显著加速45 Ca流出，但不刺激淀粉酶分泌，表明如果能量代谢受损，细胞质Ca 2+的升高不会启动分泌。CCK-PZ略微增加了42 K释放的速率系数，表明膜通透性发生了变化. CCK-PZ和乙酰胆碱的刺激作用在Na+-被Li+取代期间被抑制，表明跨膜的Na+浓度梯度在分泌中是重要的。结论：CCK‐PZ和乙酰胆碱的主要作用可能是通过改变膜通透性增加Na+流入细胞。这反过来又负责从细胞内储存（可能是内质网）释放Ca 2+，导致接近酶分泌所涉及的结构的Ca 2+浓度升高。然后分泌，如果ATP是可用的，质膜没有耗尽的Ca 2+。
1. The role of extracellular and intracellular Ca2+in pancreatic enzyme secretion has been assessed by correlating the exchange of45Ca with amylase secretion in the isolated uncinate pancreas of baby rats.2. The rate coefficient of45Ca efflux from pre‐loaded glands declined continually (indicating that45Ca is retained in several different pools) and probably reflects changes in the concentration of cytoplasmic free45Ca, which is determined by the rate at which45Ca is released from intracellular organelles into the cytoplasm.3. The rate coefficient of45Ca release was not influenced by extracellular Ca2+or Mg2+concentrations.4. Cholecystokinin‐pancreozymin (CCK‐PZ) and acetylcholine accelerated the release of both45Ca and amylase in a dose‐dependent fashion, even when extracellular Ca2+was reduced to 0·1 mM, but did not affect the initial rate of45Ca uptake by the tissue.5. In Ca2+‐free media (containing 0·5 mM‐EGTA) basal amylase secretion slowly declined and stimulated secretion was virtually abolished, but the accelerated release of45Ca was maintained.6. These observations indicate that natural stimuli of pancreatic enzyme secretion alter45Ca distribution in the cell by a process which is independent of extracellular Ca2+and which is associated with amylase secretion provided that the plasma membrane has not been depleted of Ca2+.7. Secretin, glucagon and insulin did not influence45Ca release. Secretin slightly increased amylase secretion, but this may have been a washout effect.8. Replacement of extracellular Na+by Li+increased the release of45Ca and amylase, but only in the presence of extracellular Ca2+. Li+‐substitution also increased45Ca uptake. Thus, under special conditions, secretion may be stimulated when increased amounts of Ca2+are made available from extracellular sources.9. Hyperosmolarity (known to increase45Ca release in muscle) also accelerated45Ca release and amylase secretion.10. 2,4‐Dinitrophenol markedly accelerated45Ca efflux but did not stimulate amylase secretion, indicating that a rise in cytoplasmic Ca2+will not initiate secretion if energy metabolism is impaired.11. CCK‐PZ slightly increased the rate coefficient of42K release, indicating a changed membrane permeability.12. The stimulatory effects of CCK‐PZ and acetylcholine were suppressed during Na+‐substitution by Li+, suggesting that the Na+concentration gradient across the membrane is important in secretion.13. It is concluded that the primary action of CCK‐PZ and acetylcholine may be to increase the influx of Na+into the cell by changing membrane permeability. This in turn is responsible for the release of Ca2+from intracellular stores (probably endoplasmic reticulum), leading to a rise in Ca2+concentration close to the structures involved in enzyme secretion. Secretion then follows provided that ATP is available and the plasma membrane is not depleted of Ca2+.