Influence of ANG II on cytoplasmic sodium in cultured rabbit nonpigmented ciliary epithelium

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Abstract

Angiotensin (ANG) II receptors have been reported in the nonpigmented ciliary epithelium (NPE) of the eye. In cultured NPE, we found ANG II caused a dose-dependent rise of cytoplasmic sodium. The sodium increase was inhibited by the AT1-AT2 receptor antagonist saralasin (IC50 = 3.7 nM) and the AT1 antagonist losartan (IC50 = 0.6 nM) but not by the AT2 antagonist PD-123319. ANG II also caused a dose-dependent increase in the rate of ouabain-sensitive 86Rb uptake. The ANG II-induced cell sodium increase and 86Rb uptake increase were reduced by dimethylamiloride (DMA; 10 μM). On the basis of this finding, we propose that Na+/H+ exchange is stimulated by ANG II. Simultaneously, ANG II appears to inhibit H+-ATPase-mediated proton export. Thus Ang II (10 nM) did not alter the baseline cytoplasmic pH (pHi) but reduced pHi in cells that were also exposed to 10 μM DMA. Consistent with the notion of H+-ATPase inhibition in ANG II-treated NPE, bafilomycin A1 (100 nM) (BAF) and ANG II were both observed to suppress the pHi increase that occurs upon exposure to a mixture of epinephrine (1 μM) and acetylcholine (10 μM) and the pHi increase elicited by depolarization. In ATP hydrolysis measurements, H+-ATPase activity (bafilomycin A1-sensitive ATP hydrolysis) was reduced significantly in cells that had been pretreated 10 min with 10 nM ANG II. In summary, these studies suggest that ANG II causes H+-ATPase inhibition and an increase of cell sodium due to activation of Na+/H+ exchange.

Original languageEnglish (US)
Pages (from-to)C552-C559
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number2 52-2
StatePublished - Jul 30 2002
Externally publishedYes

Keywords

  • Bafilomycin A
  • Cytoplasmic pH
  • H-ATPase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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