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 μM) elicited a prompt I sc reduction from 14.2 ± 1.2 to 10.9 ± 1.2 μA/cm 2 and increased transepithelial resistance from 0.89 ± 0.05 to 1.03 ± 0.06 kΩ · cm 2 (means ± SE, n = 21, P + 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 − /HCO 3 − exchangers. In contrast, the 5-HT-evoked effects were attenuated by the absence of Cl − (Δ I 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 + 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 2+ 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.