Geary C A, Davis C W, Paradiso A M, Boucher R C
Department of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Am J Physiol. 1995 Jun;268(6 Pt 1):L1021-8. doi: 10.1152/ajplung.1995.268.6.L1021.
Ciliated airway epithelial cells contribute to mucociliary transport systems via ciliary beating and electrolyte transport mechanisms. Both of these activities are regulated by agonists acting through intracellular calcium- and adenosine 3',5'-cyclic monophosphate (cAMP)-dependent processes (5, 15, 18, 27). This study examines the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the regulation of both ciliary beat frequency (CBF) and electrolyte transport in human airway epithelia (HAE). In a previous report, cGMP production in HAE was observed after stimulation with either C-type natriuretic peptide (CNP) or sodium nitroprusside (SNP) (6). In this study, CNP was found to increase CBF by 30 +/- 6.9%, and this effect was mimicked by the cGMP analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), but not by sodium nitroprusside. CNP-induced increases in CBF do not appear to be mediated by changes in either intracellular calcium or cAMP levels. Using modified Ussing chambers, we also investigated CNP's potential modulation of sodium and chloride transport rates. Neither CNP, nor SNP, nor 8-BrcGMP altered active ion transport rates. We conclude that CNP regulates ciliary beat via cGMP-dependent mechanisms, whereas no effect of CNP or cGMP on ion transport was detected.
纤毛气道上皮细胞通过纤毛摆动和电解质转运机制参与黏液纤毛运输系统。这两种活动均由通过细胞内钙和3',5'-环磷酸腺苷(cAMP)依赖性过程起作用的激动剂调节(5, 15, 18, 27)。本研究探讨了3',5'-环磷酸鸟苷(cGMP)在调节人气道上皮(HAE)纤毛摆动频率(CBF)和电解质转运中的作用。在先前的一份报告中,在用C型利钠肽(CNP)或硝普钠(SNP)刺激后观察到HAE中cGMP的产生(6)。在本研究中,发现CNP可使CBF增加30±6.9%,cGMP类似物8-溴-3',5'-环磷酸鸟苷(8-BrcGMP)可模拟此效应,但硝普钠则不能。CNP诱导的CBF增加似乎不是由细胞内钙或cAMP水平的变化介导的。使用改良的Ussing室,我们还研究了CNP对钠和氯转运速率的潜在调节作用。CNP、SNP或8-BrcGMP均未改变主动离子转运速率。我们得出结论,CNP通过cGMP依赖性机制调节纤毛摆动,而未检测到CNP或cGMP对离子转运有影响。