Desensitization to topical epinephrine in the rabbit eye: attenuation by dexamethasone

Desensitization of ocular adrenergic receptors was examined in vivo in albino rabbit eyes. Repeated topical administration of 2.0% l-epinephrine bitartrate (equivalent to 1.1% free base) to the rabbit eye resulted in the loss of ocular hypotensive response on the second day of daily or twice-daily treatment. Concurrent topical administration of dexamethasone phosphate (0.1%) prolonged the pressure-lowering effect of 2.0% l-epinephrine for up to 5 days. Loss of pressure-lowering response was accompanied by 100% inhibition of ciliary process beta-adrenergic-sensitive adenylate cyclase activity following 6 days of topical administration of l-epinephrine; inhibition of c-AMP synthesis was attenuated by dexamethasone (27% decrease in activity after 6 days of treatment). The data suggest that modulation of epinephrine-induced desensitization by corticosteroids in the rabbit eye is associated with stabilization of beta-adrenergic-sensitive adenylate cyclase activity.