cAMP production via the adenylyl cyclase pathway is reduced in RCS rat RPE.
cAMP production was investigated in retinal pigment epithelium (RPE) cells isolated from normal rats and from rats with an inherited retinal dystrophy (Rdy/p+). In normal RPE cells, 5'-[N-Ethylcarboxamido]-adenosine (A2 receptors) produced a fivefold increase in the level of cyclic adenosine monophosphate (cAMP) over basal levels. However, only a onefold increase in cAMP was observed in dystrophic cells. cAMP production by prostaglandins E1 and E2 (prostaglandin receptors) in dystrophic RPE cells was only 29-38% of the level observed in normal cells. Direct stimulation of adenylyl cyclase by 10 mumol/l forskolin increased cAMP levels in normal RPE cells by 90 fold over basal, but only by sixfold in the dystrophic cells. These data suggest there may be a defect in the adenylyl cyclase signaling pathway in dystrophic RPE cells.
Gregory
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Jules Stein Eye Institute, UCLA School of Medicine 90024-7008.
Abrams
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Hall
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004195:Disease Models, Animal; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D011982:Receptors, Prostaglandin / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism*; D015398:Signal Transduction; D014665:Vasodilator Agents / Q000494:pharmacology
D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000241:Adenosine