Alteration of chloride secretion across canine tracheal epithelium by lipoxygenase products of arachidonic acid.
We examined whether the leukotrienes (LT) B4, C4, D4, and E4, and 5-, 12-, and 15-hydroxyeicosatetraenoic (HETE) acids alter the electrical properties of canine tracheal epithelium. Short-circuit current (ISC) increased by 20.3 +/- 4.3 and 25.9 +/- 6.5 microA/cm2 after LTC4 and LTD4 addition, was unchanged following LTB4, LTE4, 5-, or 15-HETE addition, and was decreased by 10 +/- 3% after 12-HETE addition. LTC4- and LTD4-induced increases in ISC were dependent on the presence of Cl and were equal to the increases in net 36Cl flux toward the mucosa. The cyclooxygenase inhibitor indomethacin (10(-5) M) or the phospholipase inhibitor mepacrine (10(-5) M) diminished increases in ISC. The release rate of prostaglandins E2 and F2 alpha and thromboxane B2 rose from 8.2 +/- 2.3, 2.3 +/- 0.5, and 1.1 +/- 0.5 to 15.5 +/- 3.3, 6.0 +/- 1.4, and 4.0 +/- 0.8 ng . cm-2 . h-1, respectively, after LTC4 addition, and from 6.9 +/- 1.4, 2.5 +/- 1.1, and 1.7 +/- 1.3 to 20.2 +/- 3.1, 10.5 +/- 3.1, and 5.2 +/- 2.4 ng . cm-2 . h-1, respectively, after LTD4 addition. The release rates of 6-keto-prostaglandin F1 alpha were unchanged. A thromboxane A2 mimetic, U46619, failed to increase ISC and thromboxane synthetase inhibitors OKY-046 and dazmegrel failed to inhibit the induced increases in ISC, suggesting that thromboxane has little effect on ISC. Thus lipoxygenase products of arachidonic acid can modulate Cl secretion by the canine tracheal epithelium and do so through the release of cyclooxygenase products, including prostaglandins E2 and F2 alpha.
Leikauf
G D
GD
Ueki
I F
IF
Widdicombe
J H
JH
Nadel
J A
JA
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007474:Ion Exchange; D007477:Ions; D008084:Lipoxygenase / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D013189:SRS-A / Q000494:pharmacology*; D014132:Trachea / Q000378:metabolism*
D001095:Arachidonic Acids; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007477:Ions; D011453:Prostaglandins; D013189:SRS-A; D008084:Lipoxygenase