Activation of the basolateral Cl- conductance by cAMP in rabbit renal proximal tubule S3 segments

Pflugers Arch. 1995 May;430(1):88-95. doi: 10.1007/BF00373843.

Abstract

The regulatory mechanism of basolateral Cl- conductance in rabbit renal proximal tubule S3 segments was investigated with conventional and Cl- sensitive microelectrodes. After the basolateral Cl-/HCO3- exchanger was blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) we increased the bath K+ concentration from 5 mmol/l to 20 mmol/l, which depolarized the cells and thereby increased intracellular Cl- activity ([Cl-]i). This [Cl-]i response was enhanced by +63% in the presence of forskolin (20 mumol/l), by +40% in the presence of dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) (1 mmol/l) and by +44% in the presence of parathyroid hormone (PTH, 10 nmol/l), whereas it was inhibited by a Cl- channel blocker, indanyl-oxyacetic acid (IAA-94, 0.3 mmol/l). In addition, forskolin, PTH and chlorophenylthio-cAMP enhanced the electrogenic response to removal of bath Cl- after the blockade of K+ conductance, and this activation was also sensitive to IAA-94. On the other hand, 2 mumol/l ionomycin and 0.5 mumol/l phorbol myristate failed to activate the [Cl-]i response to elevation of bath K+ concentration and the electrogenic response to Cl- removal, and ionomycin had no effect even in the absence of DIDS. These results indicate that this basolateral Cl- conductance can be activated by cAMP, while neither the increase in cytosolic Ca2+ nor the activation of protein kinase C has direct effects on this conductance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Animals
  • Bucladesine / pharmacology
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Chlorides / metabolism*
  • Colforsin / pharmacology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology*
  • Diuretics / pharmacology
  • Female
  • Glycolates / pharmacology
  • In Vitro Techniques
  • Ion Transport
  • Ionomycin / pharmacology
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Membrane Potentials
  • Parathyroid Hormone / pharmacology
  • Protein Kinase C / agonists
  • Rabbits
  • Sodium Chloride / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thionucleotides / pharmacology
  • Uricosuric Agents / pharmacology

Substances

  • Chloride Channels
  • Chlorides
  • Diuretics
  • Glycolates
  • Parathyroid Hormone
  • Thionucleotides
  • Uricosuric Agents
  • Colforsin
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Sodium Chloride
  • MK 473
  • Ionomycin
  • Bucladesine
  • Cyclic AMP
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid