title: Atriopeptin, sodium azide and cyclic GMP reduce secretion of aqueous humour and inhibit intracellular calcium release in bovine cultured ciliary epithelium.
abstract: This study examined the involvement of cyclic GMP, protein kinase G and intracellular Ca2+ movements in the modulation of aqueous humour formation. 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 nontransformed, cultured ciliary epithelium. 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. ATP (100 microM) 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 microM; phosphodiesterase inhibitor). KT-5823 blocked the suppression of the peak Ca2+ response but not suppression of the plateau. Arterial perfusion of ATP (0.1-100 microM) produced a concentration-dependent decrease in aqueous humour formation. 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+.
authors.affiliation: Ocular Pharmacology Laboratory, Institute of Biomedical and Life Sciences, Glasgow University, Scotland, UK.
authors.forename: M
authors.initials: M
authors.lastname: Shahidullah
authors.forename: W S
authors.initials: WS
authors.lastname: Wilson
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011758:Pyrroles / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C073601:KT 5823; C016276:8-bromocyclic GMP; C057416:KT 5720; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D006152:Cyclic GMP; D002118:Calcium