The phagocytosis of rod outer segments is inhibited by drugs linked to cyclic adenosine monophosphate production.
OBJECTIVE
To study the effect of drugs that increase intracellular cyclic adenosine monophosphate on the ability of rat retinal pigment epithelial cells to phagocytize rod outer segments (ROS).


METHODS
Cultured rat retinal pigment epithelial cells were treated with cholera toxin, forskolin, isoproterenol, or isobutylmethylxanthine and the phagocytosis of ROS by such treated cells was compared to that of control specimens.


RESULTS
All of the drugs examined inhibited the ingestion, but not the binding of ROS by cultured retinal pigment epithelial cells. Cell viability was not compromised by the drug treatment because they rapidly recovered their ability to ingest ROS when the drug was removed. Dose-response curves for the inhibition of ROS phagocytosis by forskolin and isoproterenol demonstrated that this process is exquisitely sensitive to these agonists, with an IC50 for these drugs of 33 nmol/l. The results showed no measurable quantitative correlation between cyclic adenosine monophosphate levels and the inhibition of ROS phagocytosis.


CONCLUSIONS
Results showed that the ingestion of ROS by retinal pigment epithelial cells was inhibited by agents that increase intracellular cyclic adenosine monophosphate, but seems to be independent of the level of this second messenger. Alternatively, ROS phagocytosis may be exquisitely sensitive to changes in the intracellular concentration of cyclic adenosine monophosphate, which are too small to measure by available methods.
Hall
M O
MO
Jules Stein Eye Institute, UCLA School of Medicine.
Abrams
T A
TA
Mittag
T W
TW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012374:Rod Cell Outer Segment / Q000187:drug effects / Q000378:metabolism*
D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine