Dillingham M A, Anderson R J
Department of Medicine, Veterans Administration Medical Center, Denver, Colorado.
Am J Physiol. 1988 Nov;255(5 Pt 2):F841-6. doi: 10.1152/ajprenal.1988.255.5.F841.
Although guanosine 3',5'-cyclic monophosphate (cGMP) is present in renal nephron segments, there is no information on the role of cGMP as a mediator of renal tubular transport events. We found that an activator of guanylate cyclase (nitroprusside) and 8-bromocGMP (8-BrcGMP) significantly increased hydraulic conductivity in rabbit and rat cortical collecting tubules (CCT) perfused in vitro. The effect of 10(-4) M 8-BrcGMP to increase CCT hydraulic conductivity was reversible and comparable in magnitude and time course to that produced by maximal concentrations of arginine vasopressin. In rabbit CCT, cGMP increased hydraulic conductivity in the presence of phosphodiesterase inhibition with methylisobutylxanthine and in the presence of supramaximal concentrations of arginine vasopressin. Neither nitroprusside nor 8-BrcGMP stimulated adenylate cyclase activity in microdissected CCT. These data demonstrate that cGMP can act independently of either stimulation of adenylate cyclase activity or inhibition of phosphodiesterase activity to increase hydraulic conductivity in the mammalian CCT.
尽管3',5'-环磷酸鸟苷(cGMP)存在于肾单位各节段中,但关于cGMP作为肾小管转运过程介质的作用尚无相关信息。我们发现,鸟苷酸环化酶激活剂(硝普钠)和8-溴环磷酸鸟苷(8-BrcGMP)可显著增加体外灌注的兔和大鼠皮质集合管(CCT)的水通透率。10⁻⁴ M 8-BrcGMP增加CCT水通透率的作用是可逆的,其幅度和时间进程与最大浓度精氨酸加压素所产生的作用相当。在兔CCT中,cGMP在存在甲基异丁基黄嘌呤抑制磷酸二酯酶以及存在超最大浓度精氨酸加压素的情况下均可增加水通透率。硝普钠和8-BrcGMP均未刺激显微解剖的CCT中的腺苷酸环化酶活性。这些数据表明,cGMP可独立于腺苷酸环化酶活性刺激或磷酸二酯酶活性抑制而发挥作用,以增加哺乳动物CCT的水通透率。