Am. J. Respir. Cell Mol. Biol., Vol 10, No. 3, 03 1994, 322-330.
Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles
K Matsumoto, H Aizawa, R Inoue, S Hamano, S Ikeda, Z Xie, M Hirata, N Hara and Y Ito
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
We investigated the effects of cultured epithelial cells and supernatants
on resting membrane potential and excitatory neuroeffector transmission in
smooth muscle cells of dog trachea and bronchioles. The mean resting
membrane potential of the mucosa-free tracheal smooth muscle cells was
-59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (>
2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential
of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also
increased the resting membrane potential of the mucosa-free tracheal smooth
muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified
by indomethacin (10(-5) M), l- NG-nitroarginine (10(-5) M), or
oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M).
The supernatants of the cultured epithelial cells completely or partially
suppressed the contractile response of epithelium-denuded bronchioles to
electrical field stimulations and suppressed the amplitude of excitatory
junction potentials of the trachealis evoked by electrical field
stimulations. Indomethacin prevented the inhibitory effect of supernatants
on the amplitude of twitch contractions and excitatory junction potentials
and markedly suppressed supernatant-associated inhibition of the excitatory
neuroeffector transmission. Furthermore, indomethacin with AA861, a
lipoxygenase inhibitor, completely suppressed this effect. Our findings
suggest that cultured airway epithelial cells spontaneously release at
least two factors. One factor selectively modulates the resting membrane
potential, and the other inhibits the excitatory neuroeffector
transmission.
