cAMP stimulates corneal endothelial HCO − 3 transport

A previous study has demonstrated that corneal endothelial HCO − 3 transport is stimulated by the non‐specific phosphodiesterase (PDE) inhibitor IBMX. The objective of this study was to use more specific inhibitors of PDE isoenzymes to resolve which cyclic nucleotide is responsible for the observed effect of IBMX. Rolipram, an inhibitor of cAMP hydrolysing PDE, and Zaprinast, an inhibitor of cGMP hydrolysing PDE, were added to de‐epithelialized corneas mounted in vitro in modified Ussing‐type chambers. Trans‐endothelial potential difference (Pd e ), resistance (R e ) and short circuit current (SCC) were measured. To determine if Rolipram and Zaprinast increased cyclic nucleotide concentrations the intracellar concentrations of cAMP and cGMP were also determined. Rolipram (0.1 mM) significantly increased SCC in a transient manner. The maximum stimulated value for SCC was 16 ± 3% above control (mean ± SEM, n = 4). Rolipram also increased [cAMP] i from782 ± 29 to 2167 ± 111 pM mg −1 protein (mean ± SEM, n = 36). Zaprinast (0.5 mM) reversibly reduced SCC by 9 ± 3% (mean ± SEM, n = 3) and did not change [cGMP] i which measured 370 ± 15 pM mg −1 protein (mean ± SEM, n = 36). Neither drug affected R e . These results demonstrate that PDE induced elevation of [cAMP] i can increase corneal endothelial HCO − 3 transport and that cGMP is apparently unchanged and without effect.