Thromboxane A2 mimetic U46619 stimulates ciliary motility of rabbit tracheal epithelial cells.
To elucidate whether thromboxane A2 (TxA2), one of the important arachidonic acid metabolites that may play a role in the development of airway inflammation, affects respiratory ciliary motility and, if so, what the mechanism of action is, we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium in response to U46619, a TxA2 mimetic agonist, by a photoelectric method. Addition of U46619 (10(-5) M) increased CBF from 17.7 +/- 0.7 to 22.8 +/- 1.4 Hz (mean +/- SE, p less than 0.01) within 5 min, which was followed by a decline to the baseline value by 10 min. This effect was concentration-dependent, the maximal increase from the baseline value and the drug concentration required to produce a half-maximal effect (EC50) being 26.9 +/- 4.6% (p less than 0.01) and 3 x 10(-7) M, respectively. The U46619-induced increase in CBF was abolished by SQ29548, and TxA2 receptor antagonist, and inhibited by verapamil, a Ca(2+)-entry blocker, and H-7, a protein kinase C inhibitor. These results suggest that TxA2 stimulates ciliary motility through the activation of airway epithelial TxA2 receptors, and that this effect may be exerted from Ca(2+)-influx and protein kinase C.
Chiyotani
A
A
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Sakai
N
N
Isono
K
K
Kondo
M
M
Konno
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009068:Movement / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007546:Isoquinolines; D010879:Piperazines; D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C045749:SQ 29548; D014700:Verapamil; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol