Cell signal transduction mechanism for nitric oxide regulating lymphatic stomata and its draining capability.
We have previously demonstrated that nitric oxide (NO) is involved in the regulation of the lymphatic stomata. However, the related mechanisms are still unknown. The present study was designed to test the hypothesis that NO-cyclic guanosine monophosphate (cGMP) -mediated cytosolic Ca(2+) concentration ([Ca(2+)]i) signaling may contribute to the regulation of the lymphatic stomata and lymph drainage. Using trypan blue as a tracer, the effects of NO-cGMP-Ca(2+) signal cascade on the lymphatic stomata and lymph absorption were examined by means of scanning electron microscopy. Then, the role of NO in cGMP and [Ca(2+)]i of rat peritoneal mesothelial cells (RPMCs) was measured by radioimmunoassay and a confocal laser scanning microscope. Our results showed that NO-donor spermine/nitric oxide complex (Sper/NO) could broaden the opening area of the lymphatic stomata and enhance lymph absorption in a dose-dependent manner. These NO-mediated changes could be blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), a specific inhibitor of soluble guanylyl cyclase, and mimicked by calcium channel blocker nifedipine. Furthermore, Sper/NO enhanced the cGMP level and lessened [Ca(2+)](i) in RPMCs, which was completely abrogated at the presence of ODQ. Nifedipine induced an immediate and marked decrease of [Ca(2+)](i) in the RPMCs, which was not attenuated by addition of Sper/NO, indicating that the Sper/NO-cGMP signaling system induced [Ca(2+)](i) change was related to the L-type voltage-gated calcium channel in the RPMCs. Our results suggest that NO enlarges the opening area of the lymphatic stomata to strengthen the lymph drainage of tracer by means of NO-cGMP-[Ca(2+)]i signal transduction pathway in the RPMCs.
Li
Yan-Yuan
YY
Institute of Cell Biology, Zhejiang University, Hangzhou, PR China.
Li
Ji-Cheng
JC
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D003964:Diaphragm / Q000502:physiology; D008196:Lymph / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D054048:Peritoneal Stomata / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D006152:Cyclic GMP