Involvement of a signal transduction mechanism in ATP-induced mucin release from cultured airway goblet cells.
Release of mucins from cultured airway surface epithelial cells can be stimulated by extracellular ATP via a P2-purinergic receptor-mediated mechanism (K. C. Kim and B. C. Lee. 1991. Br. J. Pharmacol. 103:1053-1056). In this report, we studied the mechanism by which extracellular ATP induces the mucin release. We found that: (1) ATP increased both mucin release and generation of inositol phosphates in a dose-dependent fashion, and their dose-effect relationships were almost superimposed; (2) the increases in both mucin release and the phosphatidylinositol phosphate (PI) turnover by extracellular ATP were partially, but almost equally, blocked by the pretreatment with pertussis toxin (42% for mucin release and 44% for PI turnover). We conclude that in cultured airway goblet cells extracellular ATP stimulates mucin release by a signal transduction mechanism, which seems to involve coupling of ATP-activated P2 purinoceptors with phospholipase C, at least in part, via pertussis toxin-sensitive GTP-binding proteins. This may be an important finding in understanding the regulation of mucin release by airway goblet cells, since a number of agents present in the airway could influence this signal transduction pathway and subsequently modulate the mucin secretion.
Kim
K C
KC
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore, MD 21201.
Zheng
Q X
QX
Van-Seuningen
I
I
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D008647:Mesocricetus; D009077:Mucins / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism; D015398:Signal Transduction; D014132:Trachea / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D009077:Mucins; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins