Distinct profiles of phosphodiesterase isozymes in cultured cells derived from nonpigmented and pigmented ocular ciliary epithelium.
Alterations in either cyclic AMP (cAMP) or cyclic GMP (cGMP) may modulate the production of aqueous humor by the ciliary epithelium of the eye, thereby affecting intraocular pressure. We have found distinct profiles of phosphodiesterase (PDE) isozyme activity in cultured cells derived from bovine pigmented ciliary epithelium (PE) and cells derived from human nonpigmented ciliary epithelium (NPE), as well as corresponding differences in the effects of selective PDE inhibitors on the accumulation of cAMP and cGMP. In NPE cells, but not in PE cells, the major peak of PDE activity was stimulated by Ca++/calmodulin-stimulated (PDE I), and hydrolyzed both cAMP and cGMP. In contrast, PE cells contained a cGMP-specific PDE V not found in NPE cells. Rolipram, a selective inhibitor of PDE IV, was more potent and effective than the selective PDE III inhibitor CI-930 at potentiating intracellular cAMP accumulation in both cell types. Zaprinast, a selective inhibitor of PDE V, potentiated cGMP accumulation in PE but not in NPE cells. The results suggest that selective PDE inhibitors may modulate aqueous humor production by pigmented and nonpigmented ciliary epithelium, the two cell types may have different functional roles, and selective modulation of their functions may be possible. Furthermore, there may be distinct roles for intracellular calcium in regulating cGMP and cAMP in pigmented vs. nonpigmented ciliary epithelial cells.
Bode
D C
DC
Department of Vascular and Biochemical Pharmacology, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania.
Hamel
L T
LT
Wax
M B
MB
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000302:isolation & purification / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002461:Cell Line, Transformed; D002924:Ciliary Body / Q000166:cytology / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004357:Drug Synergism; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000201:enzymology*; D011688:Purinones / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram
D007527:Isoenzymes; D011688:Purinones; D011724:Pyridazines; D011760:Pyrrolidinones; C042528:4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP; D020889:Rolipram; D002118:Calcium