Response of rabbit ciliary process cyclic nucleotides to specific phosphodiesterase inhibitors.

PURPOSE: To determine which cyclic nucleotide phosphodiesterase family activities can be identified in rabbit ciliary processes.

METHODS

Freshly excised rabbit ciliary processes were incubated in vitro with family selective phosphodiesterase inhibitors in the absence or presence of activators of soluble or membrane bound guanylate cyclase. The resulting increases of cyclic AMP and cyclic GMP were measured by RIA.

RESULTS

Rabbit ciliary process cyclic AMP levels were increased by the phosphodiesterase 1 and 4 selective inhibitors, 8-methoxymethyl-IBMX and rolipram, respectively. Cyclic GMP levels were increased by 8-methoxymethyl-IBMX; whereas the phosphodiesterase 5 and 6 selective inhibitor, zaprinast, increased cyclic GMP little. Nitric oxide donors increased cyclic AMP in addition to cyclic GMP, and inhibition of soluble guanylate cyclase eliminated the increase of cyclic AMP. The effects of sodium nitroprusside and the phosphodiesterase 3 selective inhibitor, cilostamide, on cyclic AMP were not additive suggesting that the sodium nitroprusside mediated increase of cyclic GMP, like cilostamide, inhibited phosphodiesterase 3.

CONCLUSIONS

Cyclic AMP in rabbit ciliary processes is hydrolyzed primarily by phosphodiesterases 1 and 4, and, when cyclic GMP levels are low, by phosphodiesterase 3; cyclic GMP is hydrolyzed primarily by phosphodiesterase 1.