P81: Intracellular Ca²⁺ homeostasis regulated by a novel synergism between H₂S and no in rat pancreatic acinar cell

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• 作者：Amira Moustafa^a ; ^b ; Yoshiaki Habara^a
• 刊名：Nitric Oxide
• 出版年：30 May 2014
• 年：2014
• 卷：39
• 期：supp_S
• 页码：S40
• 全文大小：43 K

文摘

The present study was carried out to explore the effects of H₂S on Ca²⁺ homeostasis in rat pancreatic acini.

Methods

Ca²⁺ and NO imaging was applied.

Results

NaHS induced a biphasic increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in a dose-dependent manner. The NaHS-induced [Ca²⁺]_i elevation persisted with an EC₅₀ of 73.3 渭M in the absence of extracellular Ca²⁺ but was totally abolished by thapsigargin, indicating that both Ca²⁺ entry and Ca²⁺ release are involved in the increase. Similarly, endogenous H₂S precursor L-cysteine caused a concentration-dependent increase in [Ca²⁺]_i via activation of CBS enzyme. NaHS-induced [Ca²⁺]_i increase was inhibited in the presence of L-NMMA or cPTIO, and DAF-2/DAF-2T fluorometry demonstrated that NO was also produced by H₂S in a dose-dependent manner with an EC₅₀ of 64.8 渭M, indicating that NO was involved in the H₂S effect. The H₂S-induced [Ca²⁺]_i increase was inhibited by pretreatment with U73122, xestospongin C, ODQ, KT5823, and GP2A, indicating that PLC, the IP₃ receptor, soluble guanylate cyclase, protein kinase G and G_q-protein play roles as intermediate components in the H₂S-triggered intracellular signaling.

Conclusion

To our knowledge, our study is the first one highlighting the effect of H₂S on intracellular Ca²⁺ dynamics in pancreatic acinar cells. Moreover, a novel cascade was presumed to function via the synergistic interaction between H₂S and NO.