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 microM) elicited a prompt I(sc) reduction from 14.2 +/- 1.2 to 10.9 +/- 1.2 microA/cm(2) and increased transepithelial resistance from 0.89 +/- 0.05 to 1.03 +/- 0.06 kOmega. 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(-)/HCO(3)(-) 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(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.
Alvarez
L J
LJ
Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York 10029, USA. larry.alvarez@mssm.edu
Turner
H C
HC
Zamudio
A C
AC
Candia
O A
OA
D000818:Animals; D002118:Calcium / Q000502:physiology; D002712:Chlorides / Q000037:antagonists & inhibitors*; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity; D017097:Electric Impedance; D004573:Electrolytes / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D002712:Chlorides; D004573:Electrolytes; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000242:Cyclic AMP; D002118:Calcium