EFFECT OF BETA-ADRENERGIC AGENTS ON INTRACELLULAR POTENTIAL OF RABBITCILIARY EPITHELIUM

Purpose. To study the effects of beta-adrenergic agents on intracellul ar potential (Vm) of the isolated and intact rabbit ciliary epithelium . Methods. Vm was measured on the isolated intact ciliary epithelium s uperfused with adrenergic agents and cyclic AMP modulators. Results. T he nonselective beta-adrenergic agonist isoproterenol depolarized Vm i n a dose-dependent fashion, beta-adrenergic antagonists alone had no e ffect on baseline Vm. The isoproterenol response was blocked by the no nselective antagonist timolol (5 x 10(-5) M). The selective beta(2)-an tagonist ICI 118-551 caused a greater inhibition (IC50 similar to 7 x 10(-7)) than the selective beta(1)-antagonist betaxolol (IC50 similar to 6 x 10(-6)). The isoproterenol response was also significantly (p < 0.03) blocked by the nonselective alpha-antagonist phentolamine. Cycl ic AMP and phosphodiesterase inhibitors significantly decreased Vm. Pr etreatment with these inhibitors potentiated the agonist-induced depol arization. Barium, a blocker of Ca2+-sensitive K+ channels, significan tly decreased baseline Vm. Barium pretreatment blocked the beta-agonis t and cAMP induced depolarization of Vm, suggesting that the K+ curren t is necessary for the observed isoproterenol response. Pretreatment w ith the cotransport inhibitor bumetanide had no effect on the isoprote renol-induced response. Conclusions. The beta-adrenergic agonist isopr oterenol affects ionic transport precesses across the ciliary epitheli um (beta(2)> beta(1)). This effect is likely mediated through adenylat e cyclase coupled to adrenoreceptors and requires the presence of the K+ current. Blockage of the isoproterenol-induced decrease in Vm by a nonselective alpha-adrenergic antagonist indicates an interaction betw een the two adrenergic systems in the ciliary epithelium.