Eicosanoid production in isolated perfused lungs stimulated by calcium ionophore A23187.
The patterns of lung eicosanoid production were investigated in five different species by stimulating isolated lungs with calcium ionophore A23187 (10(-5) M). The species studied were the rat, ferret, hamster, guinea pig, and rabbit. The eicosanoids measured included the cyclooxygenase metabolites 6-keto-PGF1 alpha, TxB2, and PGE2 and the lipoxygenase metabolites LTC4, LTD4, and LTB4. Since these metabolites are either retained in the lungs or released into the perfusate, eicosanoids were measured in lung tissue and in the perfusate. In all animal species, calcium ionophore stimulated the production of all the eicosanoid metabolites measured, although in different relative proportions and quantities. The sulfidopeptide LTC4 was predominantly retained in the lung tissue while other eicosanoids were distributed more evenly between tissue and perfusate, with tissue levels generally being higher. The ferret lung produced large quantities of eicosanoids, more than 90% being lipoxygenase products. In contrast, the guinea pig lung produced predominantly cyclooxygenase products, especially TxB2. The rat, hamster, and rabbit lungs showed a more even distribution of cyclooxygenase and lipoxygenase products. Species differences in the ability to produce lipid mediators in the lung may be important in determining the vasoconstrictive, bronchoconstrictive, or inflammatory response to physiologic stimuli.
Westcott
J Y
JY
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
McDonnell
T J
TJ
Bostwick
P
P
Voelkel
N F
NF
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000096:biosynthesis*
D015289:Leukotrienes; D011453:Prostaglandins; D000001:Calcimycin; D013929:Thromboxane B2