Distinct profiles of phosphodiesterase isozymes in cultured cells derived from nonpigmented and pigmented ocular ciliary epithelium

D. C. Bode, L. T. Hamel, M. B. Wax

Research output: Contribution to journalArticle

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Abstract

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 Cl-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.

Original languageEnglish (US)
Pages (from-to)1286-1291
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number3
StatePublished - 1993

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Phosphoric Diester Hydrolases
Isoenzymes
Cultured Cells
Epithelium
Cyclic GMP
Cyclic AMP
Phosphodiesterase Inhibitors
Type 5 Cyclic Nucleotide Phosphodiesterases
Aqueous Humor
Type 1 Cyclic Nucleotide Phosphodiesterases
Phosphodiesterase I
Type 3 Cyclic Nucleotide Phosphodiesterases
Type 4 Cyclic Nucleotide Phosphodiesterase
Rolipram
Intraocular Pressure
Epithelial Cells
Calcium

ASJC Scopus subject areas

  • Pharmacology

Cite this

Distinct profiles of phosphodiesterase isozymes in cultured cells derived from nonpigmented and pigmented ocular ciliary epithelium. / Bode, D. C.; Hamel, L. T.; Wax, M. B.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 267, No. 3, 1993, p. 1286-1291.

Research output: Contribution to journalArticle

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