Desensitization of beta-adrenergic receptors in corneal endothelium

Corneal endothelial cells in primary culture responded to isoproterenol (Iso), epinephrine (Epi), nor-epinephrine (NE), Prostaglandins E1 and E2 (PGE1, PGE2) and forskolin by increasing cyclic AMP 61, 52, 28, 14, 10, and 176-fold, respectively, over control within a 10 minute incubation period. However, when cells were preincubated with Iso for one hour, they lost 76% of their responsiveness to a subsequent Iso challenge. Iso preincubation also decreased the effectiveness of other beta-adrenergic agonists (Epi and NE), but responses to PGE1, PGE2 and forskolin remained unchanged. The decreased cyclic AMP response was associated with a loss of beta-adrenergic binding sites. The affinity of the remaining receptors was unchanged as determined by propranolol displacement of [125I] pindolol binding. This study shows that corneal endothelial cells not only respond to beta-adrenergic stimuli, but can also regulate the magnitude and duration of their response to the hormone.