胰腺腺泡细胞中[Na⁺]i的激动剂特异性调节。
Agonist-specific regulation of [Na+]i in pancreatic acinar cells.
作者信息
Zhao H, Muallem S
机构信息
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
出版信息
J Gen Physiol. 1995 Dec;106(6):1243-63. doi: 10.1085/jgp.106.6.1243.
In a companion paper (Zhao, H., and S. Muallem. 1995), we describe the relationship between the major Na+,K+, and Cl- transporters in resting pancreatic acinar cells. The present study evaluated the role of the different transporters in regulating [Na+]i and electrolyte secretion during agonist stimulation. Cell stimulation increased [Na+]i and 86Rb influx in an agonist-specific manner. Ca(2+)-mobilizing agonists, such as carbachol and cholecystokinin, activated Na+ influx by a tetraethylammonium-sensitive channel and the Na+/H+ exchanger to rapidly increase [Na+]i from approximately 11.7 mM to between 34 and 39 mM. As a consequence, the NaK2Cl cotransporter was largely inhibited and the activity of the Na+ pump increased to mediate most of the 86Rb(K+) uptake into the cells. Secretin, which increases cAMP, activated the NaK2Cl cotransporter and the Na+/H+ exchanger to slowly increase [Na+]i from approximately 11.7 mM to an average of 24.6 mM. Accordingly, secretin increased total 86Rb uptake more than the Ca(2+)-mobilizing agonists and the apparent coupling between the NaK2Cl cotransport and the Na+ pump. All the effects of secretin could be attributed to an increase in cAMP, since forskolin affected [Na+]i and 86Rb fluxes similar to secretin. The signaling pathways mediating the effects of the Ca(2+)-mobilizing agonists were less clear. Although an increase in [Ca2+]i was required, it was not sufficient to account for the effect of the agonists. Activation of protein kinase C stimulated the NaK2Cl cotransporter to increase [Na+]i and 86Rb fluxes without preventing the inhibition of the cotransporter by Ca(2+)-mobilizing agonists. The effects of the agonists were not mediated by changes in cell volume, since cell swelling and shrinkage did not reproduce the effect of the agonists on [Na+]i and 86Rb fluxes. The overall findings of the relationships between the various Na+,K+, and Cl- transporters in resting and stimulated pancreatic acinar cells are discussed in terms of possible models of fluid and electrolyte secretion by these cells.
在一篇相关论文中（Zhao, H.，和S. Muallem. 1995），我们描述了静息胰腺腺泡细胞中主要的Na⁺、K⁺和Cl⁻转运体之间的关系。本研究评估了不同转运体在激动剂刺激期间调节细胞内Na⁺浓度（[Na⁺]i）和电解质分泌中的作用。细胞刺激以激动剂特异性方式增加了[Na⁺]i和⁸⁶Rb内流。钙动员激动剂，如卡巴胆碱和胆囊收缩素，通过四乙铵敏感通道和Na⁺/H⁺交换体激活Na⁺内流，使[Na⁺]i从约11.7 mM迅速增加到34至39 mM之间。结果，NaK2Cl协同转运体受到很大抑制，而Na⁺泵的活性增加，介导了大部分⁸⁶Rb（K⁺）摄取进入细胞。增加环磷酸腺苷（cAMP）的促胰液素激活了NaK2Cl协同转运体和Na⁺/H⁺交换体，使[Na⁺]i从约11.7 mM缓慢增加到平均24.6 mM。因此，促胰液素比钙动员激动剂增加了更多的总⁸⁶Rb摄取，以及NaK2Cl协同转运体与Na⁺泵之间明显的偶联。促胰液素的所有作用都可归因于cAMP的增加，因为福斯可林对[Na⁺]i和⁸⁶Rb通量的影响与促胰液素相似。介导钙动员激动剂作用的信号通路尚不清楚。虽然细胞内钙离子浓度（[Ca²⁺]i）的增加是必需的，但这不足以解释激动剂的作用。蛋白激酶C的激活刺激了NaK2Cl协同转运体，增加了[Na⁺]i和⁸⁶Rb通量，而不会阻止钙动员激动剂对协同转运体的抑制。激动剂的作用不是由细胞体积的变化介导的，因为细胞肿胀和收缩并没有重现激动剂对[Na⁺]i和⁸⁶Rb通量的影响。本文根据这些细胞分泌液体和电解质的可能模型，讨论了静息和刺激的胰腺腺泡细胞中各种Na⁺、K⁺和Cl⁻转运体之间关系的总体研究结果。
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