Shida M, Nishikawa K, Kikuchi S
Arzneimittelforschung. 1979;29(5):807-11.
To elucidate the mechanism of the inhibitory action of 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) on water and sodium reabsorption at the renal tubules, the effect of DS-511 (4'-OH), which is similar in diuretic effect to but more water-soluble than DS-511, on the transepithelial transport of sodium and water and permeability to urea was studied in isolated toad urinary bladder. Application of DS-511(4'-OH) at concentrations above 2 x 10(-4) mol/l to the serosal side of the bladder depressed the transepithelial potential difference, short circuit current (SCC), and membrane conductance as well as the increased response of the SCC to arginine vasopressin (AVP) and cyclic AMP. The effect of DS-511 (4'-OH) applied to the mucosal side was delayed in onset and less pronounced. Neither serosal nor mucosal 10(-3) mol/l DS-511(4'-OH) depressed the increased response of the SCC to amphotericin B. 2 x 10(-4) mol/l DS-511 (4'-OH) applied to the serosal side did not affect osmotic water flow, but potentiated the increase in water flow caused by AVP. Basal urea permeability as well as the increase in urea permeability caused by AVP were depressed by serosal 10(-3) mol/l DS-511 (4'-OH). The results show that DS-511(4'-OH) has two actions, the depression of the transepithelial transport of sodium and urea, and the potentiation of the increased water permeability caused by AVP.
为阐明1,4 - 二吗啉代 - 7 - 苯基吡啶并[3,4 - d]哒嗪（DS - 511）对肾小管水和钠重吸收的抑制作用机制，在离体蟾蜍膀胱中研究了利尿作用与DS - 511相似但水溶性比DS - 511更高的DS - 511（4'-OH）对钠和水的跨上皮转运以及尿素通透性的影响。将浓度高于2×10⁻⁴mol/L的DS - 511（4'-OH）施加于膀胱浆膜侧，可降低跨上皮电位差、短路电流（SCC）和膜电导，以及SCC对精氨酸加压素（AVP）和环磷酸腺苷（cAMP）的增强反应。将DS - 511（4'-OH）施加于黏膜侧的作用起效延迟且不太明显。浆膜侧或黏膜侧10⁻³mol/L的DS - 511（4'-OH）均未降低SCC对两性霉素B的增强反应。将2×10⁻⁴mol/L的DS - 511（4'-OH）施加于浆膜侧不影响渗透水流，但增强了AVP引起的水流增加。浆膜侧10⁻³mol/L的DS - 511（4'-OH）可降低基础尿素通透性以及AVP引起的尿素通透性增加。结果表明，DS - 511（4'-OH）有两种作用，即抑制钠和尿素的跨上皮转运，以及增强AVP引起的水通透性增加。
