Modulation of corneal endothelial hydration control mechanisms by Rolipram.
Corneal stromal hydration is maintained by an active HCO3- transport mechanism located in the corneal endothelium. Whilst modulation of transport activity by changes in intracellular cAMP concentration have been noted, the site of effect is undefined. To resolve this question, the effects of Rolipram, a cAMP phosphodiesterase inhibitor, on endothelial physiology were determined. Addition of 0.1 mM Rolipram caused a threefold increase in intracellular cAMP with no change in cGMP. Associated with the increase in cAMP was a transient whole corneal thinning and a similarly transient increase in trans-endothelial potential difference, short-circuit current and resistance. The membrane potential hyperpolarized and the intracellular Na+ concentration decreased. The decreased intracellular Na+ was associated with an increased rate of Na+ extrusion between the endothelial cell and extracellular space. It is concluded that Rolipram increases the concentration of cAMP which activates the basolateral membrane Na+/K+-ATPase activity and increases net HCO3- transport. In addition there is a reduction in endothelial permeability which combined with the increase in pump activity may jointly explain the observed stromal thinning. The duplicity of responses indicates that if cAMP has a physiological role in regulating corneal hydration then it may operate on both the endothelial pump and the endothelial permeability.
Wigham
C G
CG
Department of Optometry and Vision Sciences, Cardiff University, UK. Wighamcg@cardiff.ac.uk
Turner
H C
HC
Swan
J
J
Hodson
S A
SA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D002463:Cell Membrane Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004553:Electric Conductivity; D017097:Electric Impedance; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000502:physiology*; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D020889:Rolipram / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001639:Bicarbonates; D010726:Phosphodiesterase Inhibitors; D012964:Sodium; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D020889:Rolipram