Regulation of hormone-sensitive calcium influx by the adenylyl cyclase system in renal epithelial cells

Kenichiro Kitamura, R. Tyler Miller

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

To study signaling pathways regulated by α(s) and α(i1) in renal epithelial cells, we expressed mutant, activated forms of α(s) and α(i1) in a continuous proximal tubule cell line (MCT cells). α(sQ227L) increased cAMP production, and α(i1Q204L) reduced forskolin-sensitive cAMP production. α(i1Q204L) increased and α(sQ227L) decreased bradykinin-induced Ca influx across the cell membrane, but neither mutant affected bradykinin-stimulated intracellular Ca release or basal Ca influx. Bradykinin-stimulated Ca influx was reduced by dibutyryl cAMP, isoproterenol, and forskolin. Expression of a mutant regulatory type I subunit for cAMP-dependent protein kinase with reduced affinity for cAMP and treatment with KT-5720, a specific cAMP- dependent protein kinase inhibitor, enhanced Ca influx to a degree similar to that in cells expressing α(i1Q204L). Bradykinin-stimulated c-fos mRNA expression is partially dependent on extracellular Ca. α(sQ227L) reduced and α(i1Q204L) enhanced bradykinin-stimulated c-fos expression. Consequently, in bradykinin-stimulated cells, the adenylyl cyclase system regulates Ca influx through cAMP-dependent protein kinase, but not intracellular Ca release. Furthermore, the Ca influx mechanism acts as an integrator of two signaling pathways such that Ca-dependent signals are damped by activators of adenylyl cyclase and enhanced by inhibitors of adenylyl cyclase.

Original languageEnglish (US)
Pages (from-to)328-336
Number of pages9
JournalJournal of Clinical Investigation
Volume94
Issue number1
DOIs
StatePublished - Jul 1994

Keywords

  • G protein
  • adenylyl cyclase
  • intracellular calcium
  • membrane signal transduction

ASJC Scopus subject areas

  • Medicine(all)

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