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pubmed:abstractText |
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.
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