ATP-induced mucin release from cultured airway goblet cell involves, in part, activation of phospholipase A2.
Adenosine triphosphate (ATP) has been shown to stimulate mucin release by activation of protein kinase C (PKC) following activation of phospholipase C (PLC) coupled to the P2 receptor via G-proteins. The aim of the present study was to investigate pathways downstream to the PKC activation in ATP-induced mucin release from primary hamster tracheal surface epithelial (HTSE) cells. The release of mucin was determined by chromatographic procedure after metabolic labeling of mucin with [3H]-glucosamine. The results were: i) ATP induced the release of arachidonic acid, which caused the release of mucin. Pretreatment with mepacrine (0.3 mM), a phospholipase A2 (PLA2) inhibitor, inhibited the ATP-induced arachidonic acid and mucin release. Oleoyloxyethylphosphocholine, another PLA2 inhibitor, gave similar results. ii) An activator of PKC, 4 beta-phorbol-12 alpha-myristate-13-acetate (PMA, 1 microM) induced mucin release, which was inhibited by mepacrine pretreatment. iii) Downregulation of PKC by prolonged (16 h) PMA treatment caused inhibition of ATP-induced mucin release. Treatment of PKC downregulated HTSE cells with mepacrine did not further decrease the ATP-induced mucin release. These results suggest that PLA2 is involved in ATP-induced mucin release and its activation is sequential to the PLC-PKC pathway.
Shin
C Y
CY
Jo
M J
MJ
Lee
W J
WJ
Ryu
J R
JR
Kim
K C
KC
Ko
K H
KH
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009077:Mucins / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D009077:Mucins; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine