PMID: 8603837Feb 1, 1996Paper

Prostaglandins mediate the stimulatory effects of endothelin-1 on cyclic adenosine monophosphate accumulation in ciliary smooth muscle isolated from bovine, cat, and other mammalian species

Investigative Ophthalmology & Visual Science
A A Abdel-LatifZ Ye

Abstract

To examine the effects and mechanisms of endothelin-1 (ET-1) on cyclic adenosine monophosphate (cAMP) accumulation, inositol 1,4,5-trisphosphate (IP3) production, and contraction in ciliary muscle (CM) isolated from bovine, cat and other mammalian species. Ciliary muscle was incubated in the absence and presence of ET-1 for 5 minutes. Indomethacin (Indo, 2.5 microM) and IBMX (0.1 mM) were added 10 minutes before the addition of the peptide. Cyclic AMP accumulation and prostaglandin E2 (PGE2) release were measured by radioimmunoassay, IP3 production was measured by ion-exchange chromatography, and changes in tension were recorded isometrically. First, ET-1 (0.1 microM) increased PGE2 release by 58% to 105% and cAMP accumulation by 98% to 393% in CMs isolated from bovine, cat, dog and human, and these effects were blocked completely by Indo (2.5 microM). Unlike any other species, in bovine CM, ET-1 increased IP3 production (EC50 = 17 nM) and contraction (EC50 = 13 nM), and these effects were not inhibited by Indo. Second, kinetic studies revealed that in bovine and cat CMs, ET-1 stimulated cAMP accumulation and PGE2 release in a time- and dose-dependent manner, and these effects were inhibited by Indo in a time- and dose-dependen...Continue Reading

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