Pharmacological actions of isoprostane metabolites and phytoprostanes in human and bovine pulmonary smooth muscles.
We examined the responses to various isoprostane derivatives in bovine/human airway and pulmonary arteries. All biological activity of 15-F(2t)-IsoP was lost in its two major metabolites (15-keto-15-F(2t)-IsoP and 13,14-dihydro-15-keto-15-F(2t)-IsoP). We also examined the effects of several metabolites of 15-F(2t)-IsoP synthesized within our own laboratory-both epimers of 2,3-dinor-15-F(2t)-IsoP and of 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP, as well as 20-carboxy-2,3,4,5-tetranor-15 oxo-5,6,13,14-tetrahydro-15-F(2t)-isoP)-finding none of these to have any substantial excitatory effect. Finally, several plant-derived isoprostanes ("phytoprostanes") synthesized within our laboratory elicited little or no excitatory response in these three pulmonary smooth muscle preparations. We conclude that, although isoprostane exhibit powerful constrictor effects on airway and pulmonary vascular smooth muscles, metabolic processing of those isoprostanes essentially abolishes those biological actions; also, the phytoprostanes lack any appreciable pharmacological activity on those smooth muscle preparations.
Liu
Caiqiong
C
Firestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, L-314, St. Joseph's Hospital, 40 Charlton Avenue East, Hamilton, Ontario, Canada L8N 3Z5.
Tazzeo
Tracy
T
Guy
Alexandre
A
Durand
Thierry
T
Janssen
Luke J
LJ
D000818:Animals; D002417:Cattle; D003517:Cyclopentanes / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D028421:Isoprostanes / Q000378:metabolism / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects; D014132:Trachea / Q000187:drug effects
D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D028421:Isoprostanes; C486066:phytoprostane F1; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost