Calcium efflux from an intracellular pool activated by GTP hydrolysis in cultured gastric smooth muscle.
Calcium efflux from an intracellular pool activated by GTP hydrolysis in cultured gastric smooth muscle.
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在培养的胃平滑肌中，GTP 水解激活细胞内池中的钙流出。
DOI：
10.1152/ajpgi.1994.266.3.g388
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Khalid,M
中科院分区：
文献类型：
--
作者：
Gilbert,RJ;Khalid,M
在这些研究中，我们的特点是钙运动，由于鸟苷三磷酸（GTP）水解从ATP隔离的细胞内钙池培养的胃平滑肌。GTP（1-100 μ M），当加入到ATP再生培养基中，导致浓度依赖性和不可逆的钙从细胞器钙池流出。ATP/ADP比值（8.5-155.0）的变化不影响GTP诱导的钙外流，表明GTP不是通过ATP三磷酸钙抑制钙内流而起作用的。为了评估钙的增加是否必然与GTP水解相关，用不可水解的鸟嘌呤核苷酸类似物鸟苷5 '-[β-硫代]二磷酸（GDP β S）、5'-鸟苷酰亚胺二磷酸鸟苷（GppNHp）和5 '-O-（3-硫代三磷酸）（GTP γ S）进行实验。给予GDP β S和GppNHp没有导致显著的钙外流。GTP γ S引起了一个小的稳态钙增加（20%的可水解核苷酸诱导），但不可逆地抑制所有随后的钙增加由于GTP。通过两个实验评估GTP可能改变三磷酸肌醇（IP 3）敏感性钙库中可动员钙的浓度或IP 3相关钙通道的响应性的可能性：1）预先给予浓度<或= 100 μ M的GTP对IP 3诱导的钙释放没有影响，和2）肝素，竞争性抑制IP 3与其内质网上受体的结合，但不影响GTP相关的钙增加。这些结果表明，在胃平滑肌，GTP导致钙流出从细胞内池，这是功能上独立于该池敏感的IP 3。（250字处删节）
In these studies, we have characterized calcium movement due to guanosine triphosphate (GTP) hydrolysis from an ATP-sequestered intracellular calcium pool in cultured gastric smooth muscle. GTP (1-100 microM), when added to an ATP-regenerating medium, resulted in a concentration-dependent and irreversible efflux of calcium from an organellar calcium pool. GTP-induced calcium efflux was not affected by variation of the ATP/ADP ratio (8.5-155.0), indicating that GTP did not act by inhibiting calcium influx via calcium adenosinetriphosphatase. To assess whether the calcium increase was necessarily associated with GTP hydrolysis, experiments were performed with the nonhydrolyzable guanine nucleotide analogues guanosine 5'-[beta-thio]diphosphate (GDP beta S), 5'-guanylyl imidodiphosphate guanosine (GppNHp), and 5'-O-(3-thiotriphosphate) (GTP gamma S). Administration of GDP beta S and GppNHp resulted in no significant calcium efflux. GTP gamma S caused a small steady-state calcium increase (20% of that induced by the hydrolyzable nucleotide) but irreversibly inhibited all subsequent calcium increase due to GTP. The possibility that GTP may either modify the concentration of mobilizable calcium in inositol trisphosphate (IP3)-sensitive calcium stores or the responsivity of IP3-associated calcium channels was assessed by two experiments: 1) prior administration of GTP at concentrations < or = 100 microM had no effect on IP3-induced calcium release, and 2) heparin, which competitively inhibits IP3 binding to its receptor on the endoplasmic reticulum, did not affect GTP-associated calcium increase. These results demonstrate that, in gastric smooth muscle, GTP causes calcium efflux from an intracellular pool that is functionally independent from that pool sensitive to IP3.(ABSTRACT TRUNCATED AT 250 WORDS)