Abstract
The metabolism of leukotrienes (LT) in the sheep was investigated to define markers of 5-lipoxygenase involvement in allergic responses, obtainable by noninvasive techniques. Intravenous administration of 14,15-[3H]LTC4 (0.5 μCi/kg) revealed a rapid clearance from the circulation (half time = 90 s). Circulatory metabolism was apparent, with early formation (within 1 min) of LTD4 and LTE4 shown by reverse-phase high-pressure liquid chromatography (RP-HPLC). Urinary 3H excretion comprised 10% of the original dose. [3H]LTE4 (characterized by coelution with authentic standards during RP-HPLC analysis) was observed in early urine samples. By use of a sensitive and specific RP-HPLC radioimmunoassay analysis, immunoreactive material coeluting with LTE4 was detected in urine from allergic sheep. Excretion of this material was significantly increased during antigen-induced acute bronchoconstriction in eight conscious allergic sheep [preantigen, 65.70 ± 24.27 (SE) pg; 0-1 h postantigen, 208.00 ± 71.10 pg, P < 0.05], but not during late responses. However, total postantigen LTE4 excretion (37.8-956.1 pg/8 h) was highly correlated (r = 0.976, P < 0.001) with the severity of bronchoconstriction (445.3-2,409.1% specific pulmonary resistance per hour) assessed by measurement of the area under the curve of pulmonary function plotted against time. These findings represent an important demonstration of in vivo allergen-induced peptide LT generation in a physiologically characterized animal model of prolonged allergic bronchoconstriction and further substantiate an important role for LT in this model of allergic asthma.
| Original language | English |
|---|---|
| Pages (from-to) | 1321-1327 |
| Number of pages | 7 |
| Journal | Journal of Applied Physiology |
| Volume | 68 |
| Issue number | 4 |
| State | Published - Jan 1 1990 |
| Externally published | Yes |
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Keywords
- allergic bronchoconstriction
- asthma
- metabolism
ASJC Scopus subject areas
- Endocrinology
- Physiology
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation
Cite this
Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep. / Tagari, P.; Abraham, W. M.; McGolrick, J.; Charleson, S.; Soler, M.; Ahmed, A.; Cortez, A.; Ford-Hutchinson, A. W.
In: Journal of Applied Physiology, Vol. 68, No. 4, 01.01.1990, p. 1321-1327.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep
AU - Tagari, P.
AU - Abraham, W. M.
AU - McGolrick, J.
AU - Charleson, S.
AU - Soler, M.
AU - Ahmed, A.
AU - Cortez, A.
AU - Ford-Hutchinson, A. W.
PY - 1990/1/1
Y1 - 1990/1/1
N2 - The metabolism of leukotrienes (LT) in the sheep was investigated to define markers of 5-lipoxygenase involvement in allergic responses, obtainable by noninvasive techniques. Intravenous administration of 14,15-[3H]LTC4 (0.5 μCi/kg) revealed a rapid clearance from the circulation (half time = 90 s). Circulatory metabolism was apparent, with early formation (within 1 min) of LTD4 and LTE4 shown by reverse-phase high-pressure liquid chromatography (RP-HPLC). Urinary 3H excretion comprised 10% of the original dose. [3H]LTE4 (characterized by coelution with authentic standards during RP-HPLC analysis) was observed in early urine samples. By use of a sensitive and specific RP-HPLC radioimmunoassay analysis, immunoreactive material coeluting with LTE4 was detected in urine from allergic sheep. Excretion of this material was significantly increased during antigen-induced acute bronchoconstriction in eight conscious allergic sheep [preantigen, 65.70 ± 24.27 (SE) pg; 0-1 h postantigen, 208.00 ± 71.10 pg, P < 0.05], but not during late responses. However, total postantigen LTE4 excretion (37.8-956.1 pg/8 h) was highly correlated (r = 0.976, P < 0.001) with the severity of bronchoconstriction (445.3-2,409.1% specific pulmonary resistance per hour) assessed by measurement of the area under the curve of pulmonary function plotted against time. These findings represent an important demonstration of in vivo allergen-induced peptide LT generation in a physiologically characterized animal model of prolonged allergic bronchoconstriction and further substantiate an important role for LT in this model of allergic asthma.
AB - The metabolism of leukotrienes (LT) in the sheep was investigated to define markers of 5-lipoxygenase involvement in allergic responses, obtainable by noninvasive techniques. Intravenous administration of 14,15-[3H]LTC4 (0.5 μCi/kg) revealed a rapid clearance from the circulation (half time = 90 s). Circulatory metabolism was apparent, with early formation (within 1 min) of LTD4 and LTE4 shown by reverse-phase high-pressure liquid chromatography (RP-HPLC). Urinary 3H excretion comprised 10% of the original dose. [3H]LTE4 (characterized by coelution with authentic standards during RP-HPLC analysis) was observed in early urine samples. By use of a sensitive and specific RP-HPLC radioimmunoassay analysis, immunoreactive material coeluting with LTE4 was detected in urine from allergic sheep. Excretion of this material was significantly increased during antigen-induced acute bronchoconstriction in eight conscious allergic sheep [preantigen, 65.70 ± 24.27 (SE) pg; 0-1 h postantigen, 208.00 ± 71.10 pg, P < 0.05], but not during late responses. However, total postantigen LTE4 excretion (37.8-956.1 pg/8 h) was highly correlated (r = 0.976, P < 0.001) with the severity of bronchoconstriction (445.3-2,409.1% specific pulmonary resistance per hour) assessed by measurement of the area under the curve of pulmonary function plotted against time. These findings represent an important demonstration of in vivo allergen-induced peptide LT generation in a physiologically characterized animal model of prolonged allergic bronchoconstriction and further substantiate an important role for LT in this model of allergic asthma.
KW - allergic bronchoconstriction
KW - asthma
KW - metabolism
UR - http://www.scopus.com/inward/record.url?scp=0025193664&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025193664&partnerID=8YFLogxK
M3 - Article
C2 - 2161409
AN - SCOPUS:0025193664
VL - 68
SP - 1321
EP - 1327
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 4
ER -