Effect of beta-adrenergic agents on intracellular potential of rabbit ciliary epithelium

Abstract

Purpose: To study the effects of beta-adrenergic agents on intracellular potential (Vm) of the isolated and intact rabbit ciliary epithelium.

Methods: Vm was measured on the isolated intact ciliary epithelium superfused with adrenergic agents and cyclic AMP modulators.

Results: The nonselective beta-adrenergic agonist isoproterenol depolarized Vm in a dose-dependent fashion. beta-adrenergic antagonists alone had no effect on baseline Vm. The isoproterenol response was blocked by the nonselective antagonist timolol (5 x 10(-5) M). The selective beta 2-antagonist ICI 118-551 caused a greater inhibition (IC50 approximately 7 x 10(-7)) than the selective beta 1-antagonist betaxolol (IC50 approximately 6 x 10(-6)). The isoproterenol response was also significantly (p < 0.03) blocked by the non-selective alpha-antagonist phentolamine. Cyclic AMP and phosphodiesterase inhibitors significantly decreased Vm. Pretreatment with these inhibitors potentiated the agonist-induced depolarization. Barium, a blocker of Ca(2+)-sensitive K+ channels, significantly decreased baseline Vm. Barium pretreatment blocked the beta-agonist and cAMP induced depolarization of Vm, suggesting that the K+ current is necessary for the observed isoproterenol response. Pretreatment with the cotransport inhibitor bumetanide had no effect on the isoproterenol-induced response.

Conclusions: The beta-adrenergic agonist isoproterenol affects ionic transport processes across the ciliary epithelium (beta 2 > beta 1). This effect is likely mediated through adenylate 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 between the two adrenergic systems in the ciliary epithelium.