Dai L J, Quamme G A
Department of Medicine, University Hospital--UBC Site, University of British Columbia, Vancouver, Canada.
Pflugers Arch. 1994 May;427(1-2):1-8. doi: 10.1007/BF00585935.
Peptide hormones control salt reabsorption in cortical thick ascending limb (cTAL) cells of the loop of Henle. These agonists act, in part, through alterations on intracellular Ca2+ ([Ca2+]i). Primary cell cultures were prepared from porcine kidneys using a double antibody technique (goat antihuman Tamm-Horsfall and rabbit antigoat IgG antibodies). [Ca2+]i was determined in single cells with fluorescent techniques using fura-2. Parathyroid hormone (PTH) and arginine vasopressin (AVP) transiently increased [Ca2+]i in a dose-dependent manner. [Ca2+]i maximally increased from 85 +/- 5 nmol/l to 608 +/- 99 nmol/l with PTH, 10(-6) M, and to 766 +/- 162 nmol/l with AVP, 10(-7) M. The increment in [Ca2+]i by both hormones was by intracellular Ca2+ release and entry through plasma membrane Ca2+ channels. 8-Bromo-adenosine-3',5'-cyclic monophosphate (8-BrcAMP), 10(-4) M, increased [Ca2+]i (basal 83 +/- 3 to 427 +/- 121 nmol/l) but only from internal sources as nifedipine (10 mumol), ([Ca2+]i changes: 86 +/- 4 to 390 +/- 29 nmol/l) and removal of bath Ca/+o, ([Ca2+]i changes: 84 +/- 6 to 517 +/- 142 nmol/l), were without effect on agonist-induced [Ca2+]i. Thapsigargin, 1.5 mumol, completely abolished the AVP- and cyclic adenosine monophosphate-(cAMP)-induced Ca2+ transients, and partially inhibited PTH-mediated Ca2+ transients by about 50%. Pretreatment with 8-BrcAMP inhibited the PTH and AVP responses likely through depletion of cAMP-sensitive Ca2+ stores. Activation of protein kinase C (PKC) with phorbol esters inhibited PTH and AVP responses and 8-BrcAMP-induced [Ca2+]i transients.(ABSTRACT TRUNCATED AT 250 WORDS)
肽类激素控制着髓袢升支粗段(cTAL)细胞对盐的重吸收。这些激动剂部分通过改变细胞内钙离子浓度([Ca2+]i)发挥作用。采用双抗体技术(山羊抗人Tamm-Horsfall抗体和兔抗山羊IgG抗体)从猪肾制备原代细胞培养物。使用fura-2荧光技术测定单细胞内的[Ca2+]i。甲状旁腺激素(PTH)和精氨酸加压素(AVP)以剂量依赖方式短暂增加[Ca2+]i。PTH(10-6 M)使[Ca2+]i从85±5 nmol/L最大增加到608±99 nmol/L,AVP(10-7 M)使其增加到766±162 nmol/L。两种激素引起的[Ca2+]i增加是通过细胞内钙离子释放以及通过质膜钙离子通道进入细胞实现的。10-4 M的8-溴腺苷-3',5'-环磷酸(8-BrcAMP)增加了[Ca2+]i(基础值从83±3 nmol/L增加到427±121 nmol/L),但仅来自内部来源,因为硝苯地平(10 μmol)([Ca2+]i变化:86±4 nmol/L到390±29 nmol/L)以及去除浴液中的Ca2+([Ca2+]i变化:84±6 nmol/L到517±142 nmol/L)对激动剂诱导的[Ca2+]i无影响。1.5 μmol的毒胡萝卜素完全消除了AVP和环磷酸腺苷(cAMP)诱导的钙离子瞬变,并部分抑制PTH介导的钙离子瞬变约50%。用8-BrcAMP预处理可能通过耗尽cAMP敏感的钙离子储存来抑制PTH和AVP反应。用佛波酯激活蛋白激酶C(PKC)抑制了PTH和AVP反应以及8-BrcAMP诱导的[Ca2+]i瞬变。(摘要截断于250字)