Butkus D E, Schwartz J H
Am J Physiol. 1982 Jul;243(1):C52-61. doi: 10.1152/ajpcell.1982.243.1.C52.
The effects of the reducing agent dithiothreitol (DTT) on vasopressin (AVP)-stimulated osmotic water flow and adenylate cyclase activity were studied in the urinary bladder of Bufo marinus. DTT produced concentration-dependent inhibition of the hydroosmotic water permeability response to 10 mU/ml AVP and 10 mM theophylline but did not inhibit the response to 10 mM adenosine 3',5'-cyclic monophosphate (cAMP). The inhibitory effects of DTT on AVP responsiveness were partially reversed by washing in DTT-free Ringer solution or by addition of oxidizing agents such as dehydroascorbic acid (DHA) or H2O2. The inhibitory effects of DTT were completely reversed by washing in DTT-free Ringer plus addition of DHA. In addition, the inhibitory effects of DTT on AVP-induced osmotic water flow were partially reversed by the GTP analogue 5'-guanylyl imidodiphosphate [Gpp(NH)p]. DTT also inhibited the adenylate cyclase response to AVP but did not alter the response to AVP plus Gpp(NH)p or the response to NaF. These observations suggest that the inhibitory effect of thiol compounds on AVP responsiveness may be modulated through alterations of a redox system distal to the hormone receptor but proximal to the catalytic subunit of adenylate cyclase. Inasmuch as Gpp(NH)p partially reversed the inhibitory effects of DTT on AVP-stimulated osmotic water permeability and prevented the inhibitory effect of DTT on AVP-stimulated adenylate cyclase, an effect on either GTPase or binding of GTP to the regulatory protein of adenylate cyclase is suggested by these observations.
在海蟾蜍的膀胱中研究了还原剂二硫苏糖醇（DTT）对血管加压素（AVP）刺激的渗透水流和腺苷酸环化酶活性的影响。DTT对10 mU/ml AVP和10 mM茶碱引起的水渗透通透性反应产生浓度依赖性抑制，但不抑制对10 mM腺苷3',5'-环磷酸（cAMP）的反应。通过在不含DTT的林格氏液中冲洗或添加氧化试剂如脱氢抗坏血酸（DHA）或H2O2，DTT对AVP反应性的抑制作用可部分逆转。通过在不含DTT的林格氏液中冲洗并添加DHA，DTT的抑制作用可完全逆转。此外，GTP类似物5'-鸟苷酰亚胺二磷酸[Gpp(NH)p]可部分逆转DTT对AVP诱导的渗透水流的抑制作用。DTT还抑制腺苷酸环化酶对AVP的反应，但不改变对AVP加Gpp(NH)p的反应或对NaF的反应。这些观察结果表明，硫醇化合物对AVP反应性的抑制作用可能通过激素受体远端但腺苷酸环化酶催化亚基近端的氧化还原系统的改变来调节。由于Gpp(NH)p部分逆转了DTT对AVP刺激的水渗透通透性的抑制作用，并阻止了DTT对AVP刺激的腺苷酸环化酶的抑制作用，这些观察结果提示其对GTP酶或GTP与腺苷酸环化酶调节蛋白结合的作用。
