March 1995
Volume 36, Issue 3
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Articles  |   March 1995
Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways.
Author Affiliations
  • S Kuriyama
    Jules Stein Eye Institute, UCLA School of Medicine 90024-7008.
  • M O Hall
    Jules Stein Eye Institute, UCLA School of Medicine 90024-7008.
  • T A Abrams
    Jules Stein Eye Institute, UCLA School of Medicine 90024-7008.
  • T W Mittag
    Jules Stein Eye Institute, UCLA School of Medicine 90024-7008.
Investigative Ophthalmology & Visual Science March 1995, Vol.36, 730-736. doi:
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    • Get Citation

      S Kuriyama, M O Hall, T A Abrams, T W Mittag; Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways.. Invest. Ophthalmol. Vis. Sci. 1995;36(3):730-736.

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Abstract

PURPOSE: The authors studied the involvement of cAMP-dependent second messenger systems in the inhibition of rod outer segment (ROS) phagocytosis by isoproterenol (ISO) and forskolin (FSK) using two membrane-permeant analogs of cyclic adenosine monophosphate (cAMP), the Rp and Sp diastereoisomers of cyclic adenosine 3',5' monophosphothioate (cAMPS). Rp-cAMPS is a potent competitive inhibitor of cAMP-dependent protein kinase I and II (PKA I and II), whereas Sp-cAMPS is a potent activator of these enzymes. METHODS: ROS phagocytosis was quantitated in cultured rat RPE cells using a previously described double immunofluorescence assay. RESULTS: Sp-cAMPS showed a dose-dependent inhibition of ROS phagocytosis, whereas 100 microM Rp-cAMPS had no effect on this process. Rp-cAMPS fully prevented the inhibitory effect of Sp-cAMPS and FSK but was able to prevent only partially the inhibition of ROS phagocytosis induced by ISO. Isoproterenol plus FSK showed an additive effect on the inhibition of phagocytosis, suggesting that they act at two independent sites. However, ISO plus Sp-cAMPS or FSK plus Sp-cAMPS showed no additivity. CONCLUSIONS: Results suggest that FSK inhibits ROS phagocytosis by RPE cells through a cAMP-dependent pathway, whereas ISO inhibits ROS phagocytosis by RPE cells through cAMP-dependent and cAMP-independent pathways.

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