Kip Sertac N, Smelter Molly, Iyanoye Adeyemi, Chini Eduardo N, Prakash Y S, Pabelick Christina M, Sieck Gary C
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Arch Biochem Biophys. 2006 Aug 15;452(2):102-7. doi: 10.1016/j.abb.2006.06.014. Epub 2006 Jun 30.
Cyclic ADP-ribose (cADPR) triggers sarcoplasmic reticulum (SR) Ca(2+) release in airway smooth muscle (ASM). SR Ca(2+) release is an important component of the intracellular Ca(2+) (Ca(2+)) response of ASM to agonists. Whether cADPR is endogenously produced in ASM during agonist stimulation has not been established. In this study, cADPR production was examined in acutely dissociated porcine ASM cells. ACh stimulation (> or = 1 microM) significantly increased cADPR levels, peaking between 30s and 1 min. This effect was inhibited by M(2) and M(3) muscarinic receptor antagonists. Histamine ((> or = 5 microM) increased cADPR levels to a greater extent than ACh, while diphenhydramine blocked histamine-induced cADPR elevation. Both bradykinin (100 nM) and endothelin-1 (100 nM) also increased cADPR levels to a greater extent than ACh or histamine. These results indicate that in porcine ASM, certain agonists acting via receptors increase cADPR levels. Furthermore, the extent of cADPR responses to agonist varies, possibly reflecting differences in G-protein coupling.
环磷酸腺苷核糖（cADPR）可触发气道平滑肌（ASM）肌浆网（SR）的钙离子释放。SR钙离子释放是ASM细胞内钙离子（[Ca²⁺]i）对激动剂反应的重要组成部分。目前尚未确定在激动剂刺激过程中，ASM是否内源性产生cADPR。在本研究中，对急性分离的猪ASM细胞中的cADPR生成进行了检测。乙酰胆碱（ACh）刺激（≥1μM）可显著提高cADPR水平，在30秒至1分钟之间达到峰值。该效应被M₂和M₃毒蕈碱受体拮抗剂抑制。组胺（≥5μM）比ACh更显著地提高cADPR水平，而苯海拉明可阻断组胺诱导的cADPR升高。缓激肽（100 nM）和内皮素-1（100 nM）也比ACh或组胺更显著地提高cADPR水平。这些结果表明，在猪ASM中，某些通过受体起作用的激动剂可提高cADPR水平。此外，cADPR对激动剂的反应程度各不相同，这可能反映了G蛋白偶联的差异。
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