Speake T, Yodozawa S, Elliott A C
Cell Physiology Group, School of Biol. Sci., Univ. of Manchester, UK.
Eur J Morphol. 1998 Aug;36 Suppl:165-9.
Cell-permeant weak acids and bases alter the rate of fluid and electrolyte secretion by a range of epithelia, including the exocrine glands. It is widely assumed that weak acids and bases exert these effects by participating in the ion transport mechanism, or by changing intracellular pH (pHi) and hence modulating electrolyte (ion) transporters. An alternative possibility is that these substances act by modifying the intracellular calcium signals which control fluid secretion. In the present study we have examined whether weak acids and bases modify intracellular free calcium ([Ca2+]i) in exocrine acinar cells. Alkalinization with weak bases and acidification with weak acids had quite different effects on [Ca2+]i in resting and agonist-stimulated cells. In unstimulated lacrimal, salivary or pancreatic acinar cells, acidifying the cytosol had no effect on [Ca2+]i, while cytosolic alkalinization caused a modest rise in [Ca2+]i. This alkalinization-induced increase in [Ca2+]i appears to result from Ca2+ release from agonist-sensitive stores, and was probably caused by a small increase in intracellular InsP3 levels. In contrast, [Ca2+]i decreased when intracellular alkalinization was induced during agonist stimulation. Conversely, acidifying the cytosol during agonist stimulation raised [Ca2+]i. This latter effect was particularly dramatic in pancreatic acinar cells, where cytosolic acidification also enhanced agonist-evoked [Ca2+]i oscillations. The effects of pHi on [Ca2+]i in stimulated cells could also be observed in Ca2+-free medium, indicating that pHi altered [Ca2+]i handling by the intracellular stores rather than plasmalemmal Ca2+ transport. The results suggest that modulation of agonist-evoked [Ca2+]i signalling by changes in pHi may constitute a novel mechanism by which weak acids and bases may modulate exocrine fluid and ion transport.
细胞渗透性弱酸和弱碱会改变包括外分泌腺在内的多种上皮细胞的液体和电解质分泌速率。人们普遍认为，弱酸和弱碱通过参与离子转运机制，或通过改变细胞内pH值（pHi）从而调节电解质（离子）转运体来发挥这些作用。另一种可能性是，这些物质通过改变控制液体分泌的细胞内钙信号来起作用。在本研究中，我们检测了弱酸和弱碱是否会改变外分泌腺泡细胞内的游离钙（[Ca2+]i）。用弱碱碱化和用弱酸酸化对静息和激动剂刺激的细胞中的[Ca2+]i有截然不同的影响。在未受刺激的泪腺、唾液腺或胰腺腺泡细胞中，使细胞质酸化对[Ca2+]i没有影响，而细胞质碱化会使[Ca2+]i适度升高。这种碱化诱导的[Ca2+]i升高似乎是由激动剂敏感储存库释放Ca2+导致的，可能是由细胞内肌醇三磷酸（InsP3）水平的小幅升高引起的。相反，在激动剂刺激期间诱导细胞内碱化时，[Ca2+]i会降低。相反，在激动剂刺激期间使细胞质酸化会升高[Ca2+]i。后一种效应在胰腺腺泡细胞中尤为显著，在该细胞中，细胞质酸化还增强了激动剂诱发的[Ca2+]i振荡。在无钙培养基中也能观察到pHi对受刺激细胞中[Ca2+]i的影响，这表明pHi改变了细胞内储存库对[Ca2+]i的处理方式，而不是质膜Ca2+转运。结果表明，pHi的变化对激动剂诱发的[Ca2+]i信号的调节可能构成了弱酸和弱碱调节外分泌液体和离子转运的一种新机制。
