Serotonin-elicited inhibition of Cl- secretion in the rabbit conjunctival epithelium

The effects of serotonin [5-hydroxytryptamine (5-HT)] on the transepithelial electrical properties of the short-circuited rabbit conjunctiva were examined. With this epithelium, the short-circuit current (I-sc) measures Cl- secretion plus an amiloride-resistant Na+ absorptive process. Apical addition of 5-HT (10 muM) elicited a prompt I-sc reduction from 14.2 +/- 1.2 to 10.9 +/- 1.2 muA/cm(2) and increased transepithelial resistance from 0.89 +/- 0.05 to 1.03 +/- 0.06 k Omega . cm(2) (means +/- SE, n = 21, P< 0.05). Similar changes were obtained with conjunctivae bathed without Na+ in the apical bath, as well as with conjunctivae preexposed to bumetanide with the Cl--dependent I-sc sustained by the parallel activities of basolateral Na+/H+ and Cl-/HCO3- exchangers. In contrast, the 5-HT-evoked effects were attenuated by the absence of Cl- (DeltaI(sc) = -0.5 +/- 0.2, n = 5), suggesting that reduced Cl- conductance(s) is an effect of 5-HT exposure. In amphotericin B-treated conjunctiva and in the presence of a transepithelial K+ gradient, 5-HT addition reduced K+ diffusion across the preparation by 13% and increased transepithelial resistance by 4% (n = 6, P< 0.05), indicating that an inhibition in K+ conductance(s) was also detectable. Significant electrical responses also occurred under physiological conditions when 5-HT was introduced to epithelia pretreated with adrenergic agonists or protein kinase C, phospholipase C, phosphodiesterase, or adenylyl cyclase inhibitors or after perturbation of Ca 21 homeostasis. Briefly, the conjunctiva harbors the only known Cl--secreting epithelium in which 5-HT evokes Cl- transport inhibition; receptor subtype and signal transduction mechanism were not determined.