AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 30-L37, Copyright © 1995 by American Physiological Society
Purinergic regulation of ion transport across nonciliated bronchiolar epithelial (Clara) cells
M. R. Van Scott, T. C. Chinet, A. D. Burnette and A. M. Paradiso
East Carolina University, Greenville 27858, USA.
Previous studies demonstrated that elevation of intracellular calcium
concentration ([Ca2+]i) increased electrogenic anion transport by
bronchiolar epithelia. Extracellular nucleotides were shown to elevate
[Ca2+]i and transepithelial short-circuit current (Isc) in proximal airways
epithelia. In this study purine and pyrimidine nucleotides were
investigated for their ability to regulate ion transport by rabbit
nonciliated bronchiolar epithelial (Clara) cells in culture. ATP in the
apical bath induced a concentration-dependent transient increase in [Ca2+]i
and Isc. Mean effective doses (ED50) of the responses were 10(-7) M and
10(-6) M, respectively. Transepithelial resistance (Rt) decreased. The peak
changes in Isc and Rt were 7.8 +/- 1.2 microA/cm2 and -59 +/- 14 omega.cm2
(n = 26, basal Isc = 47.4 +/- 4.3 microA/cm2 and Rt = 428 +/- 40
omega.cm2). Some preparations exhibited a small residual increase in Isc
after the initial response, but the change was not statistically
significant (delta Isc = 1.7 +/- 1.2 microA/cm2, n = 18). Addition of ATP
to the basolateral bath had no detectable effects. Purinoceptor agonists
were used to characterize the receptors mediating the change in Isc. UTP
and ATP gamma S increased Isc and inhibited subsequent stimulation by ATP.
ADP, ADP beta S, 2-methylthio-ATP, and alpha, beta-methylene-ATP had
negligible effects on the peak delta Isc and subsequent stimulation by ATP.
The ionic mechanism underlying the ATP-induced increase in Isc was
investigated with the use of specific ion-transport inhibitors and by ion
substitution.(ABSTRACT TRUNCATED AT 250 WORDS)
