P2u-purinoceptor regulation of chloride secretion in the cultured
human tracheal submucosal glands.
Yamaya, Mutsuo, Kiyohisa Sekizawa, Yasunori Kakuta, Takashi Ohrui,
Takashi Sawai, and Hidetada Sasaki.
Department of Geriatric Medicine, First Department of Internal
Medicine and Department of Pathology, Tohoku University School of
Medicine, Sendai 980 Japan
APStracts 3:0023L, 1996.
We examined the purinergic regulation of chloride secretion and
intracellular calcium ion concentration ([Ca2+]i) in the cultured
epithelial cells passaged from human tracheal submucosal glands.
Adenosine, adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate
(ADP), adenosine 5'-triphophate (ATP), uridine 5'-triphosphate (UTP)
induced transient short-circuit current (Isc) responses in a
concentration-dependent fashion. The rank order of peak Isc responses
at 10 [mu]M was UTP = ATP > ADP > AMP = adenosine.
Diphenylamine-2-carboxylate (1 mM) and 4,4'-diisothiocyano-2,2'
-stilbene disulfonate (0.5 mM), and quinidine (1 mM) inhibited
extracellular nucleotide-induced Isc responses. However, amiloride
(10 [mu]M) was without effect. Theophylline (1 mM) did not alter ATP
(10 [mu]M)-induced Isc response. Increases in Isc induced by ATP and
UTP were significantly larger than those by [alpha],b-methylene ATP,
[beta],g-methylene ATP or 2-methylthio ATP. Extracellular nucleotides
caused increases in [Ca2+]i and the rank order of [Ca2+]i responses
was same as that of Isc responses. BAPTA-AM (50 [mu]M) inhibited
extracellular nucleotides-induced increases in Isc and [Ca2+]i. These
results suggest that extracellular nucleotides induce chloride
secretion across cultured human tracheal glands via a P2u
-purinoceptor and this chloride secretion appears to be dependent on
increases in [Ca2+]i and activation of Ca-dependent K channels.
Received 28 September 1995; accepted in final form 8 January
1996.
APS Manuscript Number L288-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96