Endothelin-induced changes of second messengers in cultured human ciliary muscle cells

Shun Matsumoto, Thomas Yorio, Peggy E. Magnino, Louis Desantis, Iok Hou Pang

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Purpose. To characterize the pharmacology of endothelin-induced changes in phospholipase C (PLC) activity, intracellular calcium concentration ([Ca2+](i)), and cyclic adenosine monophosphate (cAMP) in cultured human ciliary muscle (HCM) cells. Methods. Changes in PLC activity of HCM cells were determined by production of [3H] inositol phosphates. [Ca2+](i) was determined by single-cell dynamic fluorescence ratio imaging. Radioimmunoassays were used to determine cAMP and prostaglandin E2 (PGE2) concentrations. Results. Endothelin-1 (ET-1) stimulated PLC (mean EC50 = 335 pM) and activated calcium mobilization in HCM cells. These effects were mediated by the endothelin ET(A) receptor subtype because an ET(B) receptor- selective agonist, sarafotoxin S6c, was ineffective. Additionally, effects of ET-1 were inhibited by pretreatment with a selective ET(A) antagonist. BQ610 (mean pK(i) = 9.96 for PLC). ET-1 also stimulated the production of PGE2 (mean EC50 = 12.0 nM) and cAMP (mean EC50 = 5.2 nM) by these cells. PGE2 appeared to mediate the stimulatory effect of ET-1 on adenylyl cyclase because blockade of ET-1-induced PGE2 production by 10 μM indomethacin also completely blocked the ET-1-activated cAMP production. Conclusions. ET-1 stimulated PLC and increased [Ca2+](i) in HCM cells by the ET(A) receptor subtype. ET-1 also increased cAMP production, an effect likely mediated by the enhanced production of prostaglandins.

Original languageEnglish
Pages (from-to)1058-1066
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number6
StatePublished - 1 May 1996

Keywords

  • ciliary muscle cell
  • cyclic adenosine monophosphate
  • endothelin
  • intracellular calcium
  • phospholipase C

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