P2u-purinoceptor regulation of chloride secretion in cultured human tracheal submucosal glands
Yamaya, M.; Sekizawa, K.; Kakuta, Y.; Ohrui, T.; Sawai, T.; Sasaki, H.
American Journal of Physiology 270(6 Pt 1): L979-L984
1996
ISSN/ISBN: 0002-9513 PMID: 8764223 Document Number: 460573
We examined the purinergic regulation of chloride secretion and intracellular calcium ion concentration ((Ca-2+)-i) in the cultured epithelial cells passaged from human tracheal submucosal glands. Adenosine, AMP, ADP, ATP, and UTP induced transient short-circuit current (I-sc) responses in a concentration-dependent fashion. The rank order of peak I-sc responses at 10 mu-M concentrations was UTP = ATP gt ADP gt AMP = adenosine. Diphenylamine-2-carboxylic acid (1 mM) and 4,4'-diisothiocyano-2,2'-stilbene disulfonate (0.5 mM), and quinidine (1 mM) inhibited I-sc responses induced by extracellular nucleotides. However, amiloride (10 mu-M) was without effect. Theophylline (1 mM) did not alter ATP (10 mu-M)-induced I-sc response. Increases in I-sc induced by ATP and UTP were significantly larger than those by alpha,beta-methylene ATP, beta,gamma-methylene ATP, or 2-methylthio ATP. Extracellular nucleotides caused increases in (Ca-2+)-i, and the rank order of (Ca-2+)-i responses was same as that of I-sc responses. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (50 mu-M) inhibited increases in I-sc and (Ca-2+)-i induced by extracellular nucleotides. These results suggest that extracellular nucleotides induce chloride secretion across cultured human tracheal glands via a P-2u-purinoceptor, and this chloride secretion appears to be dependent on increases in (Ca-2+)-i and activation of Ca-dependent K channels.