The effect of non-steroidal anti-inflammatory drugs on the electrical properties of cultured dog tracheal epithelial cells

Abstract

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°C, mean values for the baseline short circuit current ( I sc) and the transepithelial resistance of 65 tissue specimens from 18 dogs were 24.0 ± 3.2 μ A/cm 2 and 458 ± 128 Ω · cm 2 , respectively. These tissues had been pretreated with amiloride to abolish active Na + absorption. Under these conditions, the I sc value serves as a measure of active Cl − secretion. The results of this study revealed that the I sc across a cultured monolayer of trachea was attenuated by the tested NSAIDs, indomethacin, fulfenamic acid, mefenamic acid, aspirin, and acetaminophen, with K i's that ranged from 6.0 × 10 −5 to 2.51 × 10 −3 M. Salicylic acid had no effect on baselin I sc. 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 I sc 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.