Brem A S, Eich E, Pearl M, Taylor A
Am J Physiol. 1985 Apr;248(4 Pt 2):F594-601. doi: 10.1152/ajprenal.1985.248.4.F594.
Acidification of the medium bathing the serosal surface of the toad urinary bladder results in impairment of the water permeability response to vasopressin. The magnitude of the hydrosmotic response to a maximal concentration of either vasopressin or the cyclic nucleotide analogue 8-(p-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (C1PhS-cAMP) was progressively reduced when serosal bath pH was decreased from 8.5 to 6.5. The disulfonic stilbenes SITS and DIDS and the diuretic furosemide, agents known to interfere with anion transport and with the regulation of intracellular pH in other tissues, inhibited the water flow response to vasopressin and C1PhS-cAMP in a pH-dependent manner when added to the serosal bathing medium. Inhibition of the hydrosmotic response to 10(-5) M C1PhS-cAMP was estimated to be half-maximal at 1.5 X 10(-4) M SITS, 2 X 10(-5) M DIDS, and 1 X 10(-5) M furosemide. The degree of inhibition induced by the anion transport inhibitors varied inversely with the concentration of exogenous cyclic nucleotide. SITS, DIDS, and furosemide had no effect on either basal or vasopressin-stimulated short-circuit current at serosal pH 8.5; all three agents inhibited basal short-circuit current at pH 7.1 but had no effect on the natriferic response to vasopressin. These results are consistent with the view that changes in intracellular hydrogen ion and/or anion concentration can selectively inhibit the increase in water permeability elicited by vasopressin at a step(s) distal to the generation of cAMP.
使蟾蜍膀胱浆膜表面的灌流介质酸化会导致对血管加压素的水通透性反应受损。当浆膜浴液的pH从8.5降至6.5时,对血管加压素或环核苷酸类似物8 -(对氯苯硫基)-环3',5'-腺苷单磷酸(C1PhS - cAMP)最大浓度的渗透反应幅度逐渐降低。二磺基芪类化合物SITS和DIDS以及利尿剂速尿,这些已知会干扰其他组织中阴离子转运和细胞内pH调节的药物,当添加到浆膜灌流介质中时,会以pH依赖性方式抑制对血管加压素和C1PhS - cAMP的水流反应。据估计,在1.5×10⁻⁴ M SITS、2×10⁻⁵ M DIDS和1×10⁻⁵ M速尿时,对10⁻⁵ M C1PhS - cAMP的渗透反应抑制作用达到半数最大抑制浓度。阴离子转运抑制剂诱导的抑制程度与外源性环核苷酸的浓度呈反比。在浆膜pH 8.5时,SITS、DIDS和速尿对基础或血管加压素刺激的短路电流均无影响;在pH 7.1时,这三种药物均抑制基础短路电流,但对血管加压素的排钠反应无影响。这些结果与以下观点一致,即细胞内氢离子和/或阴离子浓度的变化可以在cAMP产生的远端步骤选择性抑制血管加压素引起的水通透性增加。