Pharmacologic profile of lipoxins A5 and B5: new biologically active eicosanoids.
In this study, we have investigated the biological activities of LxA5 and LxB5 in isolated smooth muscle preparations of the guinea pig. LxA5 slowly contracted pulmonary parenchymal strips isolated from guinea pigs in a concentration-dependent manner over the range of 0.1-2.2 microM. This bronchoconstrictor effect was not associated with release of peptide leukotrienes (i.e. LTC4, LTD4 and LTE4) and only a slight increase in thromboxane B2. Furthermore, the bronchoconstrictor effect was not blocked by lipoxygenase inhibitors, suggesting the pulmonary effect is not mediated by lipoxygenase products. However, a peptide leukotriene receptor antagonist (e.g. SK&F-104353) inhibited or reversed the LxA5 response indicating that LxA5 and the peptide leukotrienes may share the same receptor. In contrast to LxA5, LxB5 displayed no significant bronchoconstrictor effect at concentrations up to 2.2 microM. Moreover, LxA5 and LxB5 did not exert a significant endothelium-dependent vasorelaxation in aortic vascular smooth muscle as do LxA4 and LxB4. Thus, LxA5 and LxB5 display a unique biological profile which differs from LxA4 and LxB4. LxA4 may be a mediator in circulatory disease states (e.g. myocardial ischemia, circulatory shock), but LxA5 and LxB5 are not as likely candidates as mediators of disease.
Stahl
G L
GL
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Tsao
P
P
Lefer
A M
AM
Ramphal
J Y
JY
Nicolaou
K C
KC
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001685:Biological Factors / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D044045:Lipoxins; D008168:Lung / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011863:Radioimmunoassay
D001685:Biological Factors; D044045:Lipoxins; D011450:Prostaglandin Endoperoxides, Synthetic; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; C044354:lipoxin A5; C044355:lipoxin B5; D015118:Eicosapentaenoic Acid