Endothelin-1 induces stimulation of prostaglandin synthesis in cells obtained from canine airways by bronchoalveolar lavage.
Endothelin-1 (ET-1), a potent mediator released by airway epithelial cells, often exerts its effects in the lung through stimulation of arachidonic acid (AA) metabolism. To investigate its range of influence, we studied the action of ET-1 on the synthesis and release of thromboxane (TX)B2, prostaglandin (PG)D2, and histamine from canine airway cells obtained by bronchoalveolar lavage (BAL). ET-1 (10(-10), 10(-9) and 10(-8)M) stimulated production of TXB2 and PGD2 by BAL cell preparations in a dose-related manner in the absence of measurable histamine release. Release of TXB2 was 10-fold higher than that of PGD2. The effect of ET-1 on AA metabolism in alveolar macrophages was evaluated in preparations of purified (greater than 99%) cells labelled for 20-22 hrs with 3H-AA prior to stimulation. ET-1 (10(-8), 10(-7), 10(-6)M) induced significant, dose-related release of 3H-AA and its metabolites from alveolar macrophages, to levels 350% above control. These studies indicate that low levels of ET-1 can stimulate AA metabolism in resident luminal airway cells, including alveolar macrophages, and suggest that the function of these luminal cells may be modulated by the epithelium, in vivo, through the release of this peptide into the airways.
Ninomiya
H
H
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205.
Yu
X Y
XY
Hasegawa
S
S
Spannhake
E W
EW
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D006632:Histamine / Q000096:biosynthesis; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D013928:Thromboxane A2 / Q000096:biosynthesis*
D016232:Endothelins; D016718:Arachidonic Acid; D013928:Thromboxane A2; D006632:Histamine; D015230:Prostaglandin D2