Kanda K, Miyamoto N, Seo H, Ogawa K, Hatano T, Matsui N
Department of Endocrinology and Metabolism, Nagoya University, Japan.
Eur J Pharmacol. 1991 Jan 3;192(1):153-9. doi: 10.1016/0014-2999(91)90082-2.
The present study was undertaken to examine whether sulfonamide-derived diuretics affect [Arg8]vasopressin (AVP)-stimulated or atrial natriuretic peptide (ANP)-stimulated cyclic nucleotide formation in cells cultured from rat or dog kidney. In rat renal cells, all four sulfonamide-derived diuretics examined significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations of 10(-4) and 10(-3) M, while basal cAMP formation was unchanged by the diuretics. When cells were stimulated with 10(-7) M AVP, low ceiling diuretics (indapamide and trichlormethiazide) did not suppress cAMP formation, while high ceiling diuretics (furosemide and azosemide) significantly suppressed cAMP formation at concentrations of 10(-4) and 10(-3) M. The suppressive effect of the diuretics on AVP-stimulated cAMP formation in vitro paralleled the reported diuretic potency of the agents in vivo. In dog renal cells, all four diuretics significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations from 10(-6) to 10(-5) M, while these diuretics did not change basal cAMP levels. High ceiling diuretics suppressed 10(-7) M AVP-stimulated cAMP formation, whereas low ceiling diuretics did not. The difference in effective doses between rats and dogs seems to be consistent with the species difference observed in vivo. None of the diuretics affected basal levels of intracellular cGMP or ANP-stimulated cGMP formation in cultured rat renal cells. In addition to the inhibition of the Na/K/Cl co-transporter, it is suggested that most sulfonamide-derived diuretics act, at least in part, by inhibiting the actions of AVP.
本研究旨在探讨磺胺类利尿剂是否会影响[精氨酸8]血管加压素（AVP）刺激或心房利钠肽（ANP）刺激的大鼠或犬肾培养细胞中环核苷酸的形成。在大鼠肾细胞中，所检测的四种磺胺类利尿剂在10^(-4)和10^(-3) M浓度下均能显著抑制10^(-9) M AVP刺激的cAMP形成，而利尿剂对基础cAMP形成无影响。当细胞用10^(-7) M AVP刺激时，低效能利尿剂（吲达帕胺和三氯噻嗪）不抑制cAMP形成，而高效能利尿剂（呋塞米和阿佐塞米）在10^(-4)和10^(-3) M浓度下显著抑制cAMP形成。利尿剂在体外对AVP刺激的cAMP形成的抑制作用与这些药物在体内报道的利尿效能平行。在犬肾细胞中，所有四种利尿剂在10^(-6)至10^(-5) M浓度下均能显著抑制10^(-9) M AVP刺激的cAMP形成，而这些利尿剂不改变基础cAMP水平。高效能利尿剂抑制10^(-7) M AVP刺激的cAMP形成，而低效能利尿剂则无此作用。大鼠和犬之间有效剂量的差异似乎与体内观察到的种属差异一致。在培养的大鼠肾细胞中，没有一种利尿剂影响细胞内cGMP的基础水平或ANP刺激的cGMP形成。除了抑制Na/K/Cl共转运体之外，提示大多数磺胺类利尿剂至少部分是通过抑制AVP的作用来发挥作用的。
