Cyclic adenosine monophosphate-stimulated bicarbonate secretion in rabbit cortical collecting tubules.
Cyclic adenosine monophosphate-stimulated bicarbonate secretion in rabbit cortical collecting tubules.
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环磷酸腺苷刺激兔皮质集合管中的碳酸氢盐分泌。
DOI：
10.1172/jci111925
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Schuster,VL
中科院分区：
文献类型：
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作者：
Schuster,VL
本文研究了环磷酸腺苷（cAMP）对离体灌流的家兔皮质集合小管转运HCO-3的影响。在NaHCO 3负载兔的肾小管中观察到HCO-3净分泌。8-溴-cAMP-刺激净HCO-3分泌，而分泌下降，随着时间的推移，在控制小管。已知异丙肾上腺素和加压素（ADH）均刺激该上皮细胞中的腺苷酸环化酶;然而，只有异丙肾上腺素刺激HCO-3净分泌。研究了cAMP刺激HCO-3分泌的机制。如果HCO-3和H+分泌在表现出净HCO-3分泌的小管中同时发生，则cAMP可能通过抑制H+分泌、刺激HCO-3分泌或两者来增加净HCO-3分泌速率。使用二磺酸芪（4，4 '-二异硫氰基芪-2，2'-二磺酸盐（DIDS））的基底外侧添加来检查这些可能性。在NH 4Cl负载的家兔的酸化小管中，DIDS消除了HCO-3重吸收，这一结果与DIDS作为H+分泌抑制剂的已知作用一致。相反，cAMP保持酸化（H+分泌）完整。应用于HCO-3分泌小管的DIDS未能增加HCO-3分泌速率，表明HCO-3分泌小管中的H+分泌最少。因此，cAMP对H+分泌的抑制不能解释cAMP诱导的HCO-3净分泌的刺激。cAMP刺激的HCO-3分泌被0 Cl灌注液可逆地消除，而管腔DIDS没有影响。当浴[Na+]为145 mM或5 mM时，浴阿米洛利（1 mM）未能消除cAMP刺激的HCO-3分泌。cAMP使跨上皮电压去极化。cAMP后收集的液体[HCO-3]可以通过电驱动力来解释，表明cAMP刺激被动HCO-3分泌。然而，cAMP并没有改变HCO-3渗透性的条件下，预期抑制跨细胞的HCO-3运动（0 Cl-溶液和浴DIDS）测量。这测得的HCO-3的渗透性是不够高的帐户，被动扩散，在含氯溶液中观察到的HCO-3通量。我们得出以下结论：cAMP通过刺激HCO 3-分泌而不是抑制H+分泌来增加HCO 3-净分泌;这种HCO 3-分泌可能是通过Cl-HCO 3-交换发生的;在这些条件下，Na+-H+交换似乎在基底外侧H+排出中不起作用;异丙肾上腺素刺激HCO 3-分泌，而ADH不刺激，表明在这种cAMP反应中存在单独的细胞cAMP池或细胞异质性。
We studied the effects of cyclic AMP (cAMP) on HCO-3 transport by rabbit cortical collecting tubules perfused in vitro. Net HCO-3 secretion was observed in tubules from NaHCO3- loaded rabbits. 8-Bromo-cAMP-stimulated net HCO-3 secretion, whereas secretion fell with time in control tubules. Both isoproterenol and vasopressin (ADH) are known to stimulate adenylate cyclase in this epithelium; however, only isoproterenol stimulated net HCO-3 secretion. The mechanism of cAMP-stimulated HCO-3 secretion was examined. If both HCO-3 and H+ secretion were to occur simultaneously in tubules exhibiting net HCO-3 secretion, cAMP might increase the net HCO-3 secretory rate by inhibiting H+ secretion, by stimulating HCO-3 secretion, or both. These possibilities were examined using basolateral addition of the disulfonic stilbene (4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In acidifying tubules from NH4Cl-loaded rabbits, DIDS eliminated HCO-3 reabsorption, a result consistent with known effects of DIDS as an inhibitor of H+ secretion. In contrast, cAMP left acidification (H+ secretion) intact. DIDS applied to HCO-3 secretory tubules failed to increase the HCO-3 secretory rate, indicating minimal H+ secretion in HCO-3 secreting tubules. Thus, inhibition of H+ secretion by cAMP could not account for the cAMP-induced stimulation of net HCO-3 secretion. cAMP-stimulated HCO-3 secretion was reversibly eliminated by 0 Cl perfusate, whereas luminal DIDS had no effect. Bath amiloride (1 mM) failed to eliminate cAMP-stimulated HCO-3 secretion when bath [Na+] was 145 mM or 5 mM. cAMP depolarized the transepithelial voltage. The collected fluid [HCO-3] after cAMP could be accounted for by electrical driving forces, suggesting that cAMP stimulates passive HCO-3 secretion. However, cAMP did not alter HCO-3 permeability measured under conditions expected to inhibit transcellular HCO-3 movement (0 Cl- solutions and bath DIDS). This measured HCO-3 permeability was not high enough to account, by passive diffusion, for the HCO-3 fluxes observed in Cl-containing solutions. We conclude the following: cAMP increased net HCO3- secretion by stimulating HCO3- secretion and not by inhibiting H+ secretion; this HCO3- secretion may have occurred by Cl-HCO3- exchange; Na+-H+ exchange appeared not to play a role in basolateral H+ extrusion under these conditions; and the stimulation of HCO3- secretion by isoproterenol, but not ADH, suggests the existence of separate cell cAMP pools or cellular heterogeneity in this cAMP response.