The effect of non-steroidal anti-inflammatory drugs on the electrical properties of cultured dog tracheal epithelial cells.
The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the electrical properties of primary cultures of dog tracheal epithelium has been studied. The cells used were grown with an air interface in a serum-free medium on membranes coated with human placental collagen. When mounted in Ussing chambers at 37 degrees C, mean values for the baseline short circuit current (Isc) and the transepithelial resistance of 65 tissue specimens from 18 dogs were 24.0 +/- 3.2 microA/cm2 and 458 +/- 128 omega.cm2, respectively. These tissues had been pretreated with amiloride to abolish active Na+ absorption. Under these conditions, the Isc value serves as a measure of active Cl- secretion. The results of this study revealed that the Isc across a cultured monolayer of trachea was attenuated by the tested NSAIDs, indomethacin, fulfenamic acid, mefenamic acid, aspirin, and acetaminophen, with Ki's that ranged from 6.0 x 10(-5) to 2.51 x 10(-3) M. Salicylic acid had no effect on baseline Isc. The Isc sensitivity sequence to the Cl- channel inhibitors tested was: fulfenamic acid >> indomethacin > mefenamic acid >> aspirin > acetaminophen > salicylic acid. The NSAIDs also significantly inhibited both the transient, Ca(2+)-dependent and the sustained, cAMP-dependent increases in Isc elicited by isoproterenol. Thus, the tested NSAIDs appeared to have an effect on the electrical properties of the cells. A similar effect of NSAIDs on ion transport across the human airway epithelium may help to reduce airway fluid secretion.
Mochizuki
H
H
Department of Pediatrics, Gunma University School of Medicine, Japan.
Morikawa
A
A
Tokuyama
K
K
Kuroume
T
T
Chao
A C
AC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007202:Indicators and Reagents; D007545:Isoproterenol / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018118:Chloride Channels; D002712:Chlorides; D007202:Indicators and Reagents; D007545:Isoproterenol