Journal of Applied Physiology, Vol 70, Issue 5 2137-2144, Copyright © 1991 by American Physiological Society
Respiratory epithelium-dependent inhibition of protein kinase C of airway smooth muscle cells
M. Souhrada and J. F. Souhrada
John B. Pierce Foundation Laboratory, New Haven, Connecticut 06519.
We have examined the effect of phorbol myristate acetate (PMA) on airway
smooth muscle (ASM) in the presence and absence of respiratory epithelium
(RE) and analyzed the dependence of this response on extracellular sodium,
Na+/H+ exchange, calcium, and cyclooxygenase products; we determined both
the resting membrane potential and isometric force developed by ASM
preparations. Removal of RE had no effect on the values of the resting
membrane potential of ASM cells. In the presence of RE in the preparation,
both electrical and contractile responses to PMA (10(-5) M) were
significantly different compared with the response of ASM to PMA without
RE. When the RE was present, stimulation of protein kinase C caused only a
biphasic response in both membrane potential and isometric force. In either
the presence or absence of RE, amiloride (10(-5) M) and a low-sodium
solution inhibited both electrical and contractile changes of ASM cells
caused by PMA. In the presence or absence of RE, verapamil (10(-5) M)
attenuated (P less than 0.05) both electrical and contractile responses of
ASM cells as induced by PMA. Verapamil, however, had no effect on the last
phase of PMA-induced response. Pretreatment of preparations with
indomethacin (10(-6) M) changed the PMA-induced response of ASM with RE to
a response usually observed in ASM without RE. Finally, the incubation of
tracheal preparations without RE with prostaglandin E2 (10(-8) M) altered
the response of these preparations in such a way that their electrical and
contractile response to PMA was essentially identical to the PMA response
observed in preparations with an intact RE.(ABSTRACT TRUNCATED AT 250
WORDS)
