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

The effects of serotonin [5-hydroxytryptamine (5-HT)] on the transepithelia l electrical properties of the short-circuited rabbit conjunctiva were exam ined. With this epithelium, the short-circuit current (I-sc) measures Cl- s ecretion plus an amiloride-resistant Na+ absorptive process. Apical additio n 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). Sim ilar changes were obtained with conjunctivae bathed without Na+ in the apic al bath, as well as with conjunctivae preexposed to bumetanide with the Cl- -dependent I-sc sustained by the parallel activities of basolateral Na+/Hand Cl-/HCO3- exchangers. In contrast, the 5-HT-evoked effects were attenua ted by the absence of Cl- (DeltaI(sc) = -0.5 +/- 0.2, n = 5), suggesting th at reduced Cl- conductance(s) is an effect of 5-HT exposure. In amphoterici n B-treated conjunctiva and in the presence of a transepithelial K+ gradien t, 5-HT addition reduced K+ diffusion across the preparation by 13% and inc reased transepithelial resistance by 4% (n = 6, P< 0.05), indicating that a n inhibition in K+ conductance(s) was also detectable. Significant electric al responses also occurred under physiological conditions when 5-HT was int roduced to epithelia pretreated with adrenergic agonists or protein kinase C, phospholipase C, phosphodiesterase, or adenylyl cyclase inhibitors or af ter perturbation of Ca 21 homeostasis. Briefly, the conjunctiva harbors the only known Cl--secreting epithelium in which 5-HT evokes Cl- transport inh ibition; receptor subtype and signal transduction mechanism were not determ ined.