title: Activation of the basolateral Cl- conductance by cAMP in rabbit renal proximal tubule S3 segments.
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.
authors.affiliation: First Department of Internal Medicine, Tokyo University School of Medicine, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Seki
authors.forename: S
authors.initials: S
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Uwatoko
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D006016:Glycolates / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport; D015759:Ionomycin / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D010281:Parathyroid Hormone / Q000494:pharmacology; D011493:Protein Kinase C / Q000819:agonists; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014528:Uricosuric Agents / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D004232:Diuretics; D006016:Glycolates; D010281:Parathyroid Hormone; D013873:Thionucleotides; D014528:Uricosuric Agents; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D012965:Sodium Chloride; C015765:MK 473; D015759:Ionomycin; D003994:Bucladesine; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid