Watson E L, Jacobson K L, Singh J C, Ott S M
Department of Oral Biology, University of Washington, Seattle, Washington 98195, USA.
Am J Physiol. 1999 Aug;277(2):C262-70. doi: 10.1152/ajpcell.1999.277.2.C262.
Carbachol- and thapsigargin-induced changes in cGMP accumulation were highly dependent on extracellular Ca(2+) in mouse parotid acini. Inhibition of nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) resulted in complete inhibition of agonist-induced cGMP levels. NOS inhibitors reduced agonist-induced Ca(2+) release and capacitative Ca(2+) entry, whereas the inhibition of sGC had no effect. The effects of NOS inhibition were not reversed by 8-bromo-cGMP. The NO donor GEA-3162 increased cGMP levels blocked by the inhibition of sGC. GEA-3162-induced increases in Ca(2+) release from ryanodine-sensitive stores and enhanced capacitative Ca(2+) entry, both of which were unaffected by inhibitors of sGC but reduced by NOS inhibitors. Results support a role for NO, independent of cGMP, in agonist-mediated Ca(2+) release and Ca(2+) entry. Data suggest that agonist-induced Ca(2+) influx activates a Ca(2+)-dependent NOS, leading to the production of NO and the release of Ca(2+) from ryanodine-sensitive stores, providing a feedback loop by which store-depleted Ca(2+) channels are activated.
在小鼠腮腺腺泡中，卡巴胆碱和毒胡萝卜素诱导的环鸟苷酸（cGMP）积累变化高度依赖细胞外钙离子（Ca(2+)）。一氧化氮合酶（NOS）和可溶性鸟苷酸环化酶（sGC）的抑制导致激动剂诱导的cGMP水平完全抑制。NOS抑制剂降低了激动剂诱导的Ca(2+)释放和容量性Ca(2+)内流，而sGC的抑制则没有效果。8-溴-cGMP不能逆转NOS抑制的作用。一氧化氮供体GEA-3162增加了被sGC抑制所阻断的cGMP水平。GEA-3162诱导的来自兰尼碱敏感储存库的Ca(2+)释放增加以及容量性Ca(2+)内流增强，这两者均不受sGC抑制剂的影响，但被NOS抑制剂降低。结果支持了一氧化氮在激动剂介导的Ca(2+)释放和Ca(2+)内流中独立于cGMP的作用。数据表明，激动剂诱导的Ca(2+)内流激活了一种Ca(2+)依赖性NOS，导致一氧化氮的产生以及从兰尼碱敏感储存库中释放Ca(2+)，提供了一个反馈回路，通过该回路储存耗尽的Ca(2+)通道被激活。
