Barsigian C, Barbieri E J
Department of Pharmacology, Hahnemann University, Philadelphia, Pennsylvania 19102.
Cell Biochem Funct. 1990 Jul;8(3):171-5. doi: 10.1002/cbf.290080308.
Extracellular sodium is known to influence secretion by certain secretory cells, possibly by mobilizing calcium from cellular stores or by altering intracellular pH via regulation of a Na(+)-H+ antiport system. Using canine tracheal explants, we determined whether agents which alter sodium fluxes are capable of modulating basal or cholinergically-induced secretion of mucus glycoconjugates. Methacholine, a cholinergic agonist, increased mucus secretion from explants incubated in the presence or absence of calcium, but had no effect on secretion when incubated in sodium-deficient media, indicating (a) that cholinergically-induced secretion can be mediated by mobilization of cellular calcium and (b) that extracellular sodium was required for this stimulatory effect. Several agents which increase intracellular sodium were tested for their effect on mucus secretion. Ouabain, a sodium pump inhibitor, and veratridine, a sodium channel activator, did not significantly affect control or methacholine-induced secretion; gramicidin, a sodium ionophore, also had no effect on basal release. Tetrodotoxin, a sodium channel inhibitor, was also without effect on basal or methacholine-stimulated mucus release. Agents which alter intracellular pH were also examined for their effects on basal or methacholine-induced glycoconjugate secretion. Amiloride, which decreases intracellular pH by inhibiting Na(+)-H+ exchange, produced a 19 per cent increase in basal secretion (not statistically significant), but had no effect on methacholine-induced secretion. An agent, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which decreases intracellular pH by inhibiting HCO3(-)-Cl- exchange, elicited decreases in both basal and methacholine-induced secretion, but the inhibition did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
已知细胞外钠会影响某些分泌细胞的分泌，可能是通过从细胞内储存库中动员钙，或者通过调节钠氢反向转运系统来改变细胞内pH值。我们使用犬气管外植体，确定改变钠通量的试剂是否能够调节黏液糖缀合物的基础分泌或胆碱能诱导的分泌。胆碱能激动剂乙酰甲胆碱，在有或无钙的情况下孵育时，会增加外植体的黏液分泌，但在缺钠培养基中孵育时对分泌没有影响，这表明（a）胆碱能诱导的分泌可通过细胞钙的动员来介导，以及（b）这种刺激作用需要细胞外钠。测试了几种增加细胞内钠的试剂对黏液分泌的影响。钠泵抑制剂哇巴因和钠通道激活剂藜芦碱，对对照或乙酰甲胆碱诱导的分泌没有显著影响；钠离子载体短杆菌肽对基础释放也没有影响。钠通道抑制剂河豚毒素对基础或乙酰甲胆碱刺激的黏液释放也没有作用。还研究了改变细胞内pH值的试剂对基础或乙酰甲胆碱诱导的糖缀合物分泌的影响。通过抑制钠氢交换来降低细胞内pH值的氨氯地平，使基础分泌增加了19%（无统计学意义），但对乙酰甲胆碱诱导的分泌没有影响。一种通过抑制碳酸氢根氯交换来降低细胞内pH值的试剂4,4'-二异硫氰基芪-2,2'-二磺酸（DIDS），使基础和乙酰甲胆碱诱导的分泌均减少，但抑制作用未达到统计学意义。（摘要截短于250字）
