Atriopeptin, sodium azide and cyclic GMP reduce secretion of aqueous humour and inhibit intracellular calcium release in bovine cultured ciliary epithelium

Mohammad Shahidullah, William S. Wilson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

1. This study examined the involvement of cyclic GMP, protein kinase G and intracellular Ca2+ movements in the modulation of aqueous humour formation. 2. Using the bovine arterially-perfused eye preparation, drug effects on intraocular pressure and aqueous humour formation rate were measured by manometry and fluorescein dilution, respectively. Drug effects on intracellular [Ca2+] were determined by fura-2 fluorescence ratio technique in non-transformed, cultured ciliary epithelium. 3. Intra-arterial injection of atriopeptin (50 pmol) or sodium azide (10 nmol) produced significant reduction in aqueous humour formation (> 38%). This was blocked by selective inhibition (KT-5823) of protein kinase G, but not by selective inhibition (KT-5720) of protein kinase A. Reductions of intraocular pressure produced by atriopeptin or azide were almost completely blocked by KT-5823. 4. ATP (100 μM) caused rapid, transient increase in intracellular Ca2+ followed by a slow decline and prolonged plateau. This response showed concentration-dependent inhibition by atriopeptin, azide or 8-bromo cyclic GMP, and this inhibition of the rapid (peak) Ca2+ increase was enhanced by zaprinast (100 μM; phosphodiesterase inhibitor). KT-5823 blocked the suppression of the peak Ca2+ response but not suppression of the plateau. 5. Arterial perfusion of ATP (0.1-100 μM) produced a concentration-dependent decrease in aqueous humour formation. 6. Aqueous humour formation in the bovine eye can be manipulated through cyclic GMP, operating via protein kinase G. Close parallels appear when Ca2+ movements are modified by similar manipulations of cyclic GMP, suggesting that Ca2+ transients may play an important role in aqueous humour formation and that interplay occurs between cyclic GMP and Ca2+.

Original languageEnglish (US)
Pages (from-to)1438-1446
Number of pages9
JournalBritish Journal of Pharmacology
Volume127
Issue number6
DOIs
StatePublished - Aug 10 1999
Externally publishedYes

Keywords

  • ATP
  • Aqueous humour
  • Atriopeptin
  • Azide
  • Bovine ciliary epithelium
  • Cyclic GMP
  • Intracellular calcium
  • Protein kinase G

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Atriopeptin, sodium azide and cyclic GMP reduce secretion of aqueous humour and inhibit intracellular calcium release in bovine cultured ciliary epithelium'. Together they form a unique fingerprint.

  • Cite this