Desensitization of β-Adrenergic Receptors in Corneal Endothelium

Abstract

ABSTRACT

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 β-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 β-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 β-adrenergic stimuli, but can also regulate the magnitude and duration of their response to the hormone.