Moses A M, Coulson R
Endocrinology. 1980 Mar;106(3):967-72. doi: 10.1210/endo-106-3-967.
The effect of chlorpropamide was determined in Brattleboro diabetes insipidus (DI) rats that were injected with 1-deamino-8-D-arginine vasopressin (dDAVP). Chlorpropamide augmented the antidiuretic responses to 0.78 and 1.56 ng dDAVP but not to larger doses. In an effort to explain this observation we investigated the effect of chlorpropamide on renal medullary adenylate cyclase activation by dDAVP and on phosphodiesterase activity. We found that the injection of chlorpropamide increased adenylate cyclase activation by dDAVP added in vitro to renal medullary cell membrane preparations from Brattleboro DI rats but had no effect on phosphodiesterase activity. When kidneys from Brattleboro DI rats, treated and not treated with chlorpropamide, were perfused in vitro, we found that 10(-4) M dDAVP increased the concentration of cAMP in comparison to untreated and chlorpropamide-treated groups, and that chlorpropamide plus dDAVP resulted in a greater concentration of renal cAMP than was found with dDAVP alone. We believe that treatment with chlorpropamide increases dDAVP-stimulated renal medullary adenylate cyclase activity without altering phosphodiesterase activity and that this leads to increased renal cAMP concentrations. This, in turn, causes an augmented antidiuresis in response to dDAVP.
在注射了1-去氨基-8-D-精氨酸加压素（dDAVP）的布拉德福德尿崩症（DI）大鼠中测定了氯磺丙脲的作用。氯磺丙脲增强了对0.78和1.56 ng dDAVP的抗利尿反应，但对更大剂量则无增强作用。为了解释这一观察结果，我们研究了氯磺丙脲对dDAVP激活肾髓质腺苷酸环化酶以及对磷酸二酯酶活性的影响。我们发现，注射氯磺丙脲可增加体外添加到来自布拉德福德DI大鼠肾髓质细胞膜制剂中的dDAVP对腺苷酸环化酶的激活作用，但对磷酸二酯酶活性无影响。当对用氯磺丙脲处理和未处理的布拉德福德DI大鼠的肾脏进行体外灌注时，我们发现与未处理组和氯磺丙脲处理组相比，10⁻⁴ M dDAVP可增加cAMP的浓度，并且氯磺丙脲加dDAVP导致的肾cAMP浓度高于单独使用dDAVP时的浓度。我们认为，氯磺丙脲治疗可增加dDAVP刺激的肾髓质腺苷酸环化酶活性，而不改变磷酸二酯酶活性，这导致肾cAMP浓度增加。反过来，这会引起对dDAVP的抗利尿作用增强。
