Bradykinin-induced chloride conductance in murine proximal tubule epithelial cells

Manish M Tiwari, Joseph R. Stimers, Philip R. Mayeux

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Despite the recognized role of bradykinin (BK)-induced calcium and chloride conductance in regulating salt transport in the kidney, the signaling pathway involved has not been well examined. Patch clamp of murine proximal tubule (TKPTS) cells revealed that BK (10 nM) produced an increase in an outwardly rectifying current from a basal level of 2.9±0.6 to 13.8±1.1 pA/pF following addition of BK (n = 8; p<0.001). The shift in reversal potential seen with BK on changing the intracellular solution to 152 mM chloride and significant inhibition of the current by 100 μM 4,4′-di-isothiocyanato-stilbene- 2,2′-disulphonic acid (DIDS) suggested that BK activated a chloride current. BK-induced current was blocked by B2 receptor antagonist but not by B1 antagonist or pertussis toxin indicating that the current was mediated by B2 receptors possibly through Gq activation. TMB-8 completely blocked the BK-calcium rise in fura-2 studies but did not block the BK-chloride response indicating that BK-mediated chloride current is calcium-independent. BK-induced current was dependent on phospholipase C (PLC) since U73122, a PLC-β blocker (10 μM) blocked it completely. Furthermore, chloride conductance was not modulated by bisindolylmaleimide, an inhibitor of protein kinase C (PKC), but was enhanced by dibutyryl cAMP. We conclude that BK-induced rise in chloride current is mediated by B2 receptors and dependent on PLC activation but not dependent on calcium rise. Furthermore, the current can be modulated by cAMP but not PKC.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMolecular and cellular biochemistry
Volume297
Issue number1-2
DOIs
StatePublished - Mar 1 2007

Fingerprint

Bradykinin
Chlorides
Epithelial Cells
Type C Phospholipases
Induced currents
Calcium
Protein Kinase C
Chemical activation
Stilbenes
Calcium Chloride
Fura-2
Pertussis Toxin
Clamping devices
Salts
Kidney
Acids

Keywords

  • Bradykinin
  • Chloride current
  • Proximal tubule

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Bradykinin-induced chloride conductance in murine proximal tubule epithelial cells. / Tiwari, Manish M; Stimers, Joseph R.; Mayeux, Philip R.

In: Molecular and cellular biochemistry, Vol. 297, No. 1-2, 01.03.2007, p. 1-8.

Research output: Contribution to journalArticle

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