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The in vivo production of peptide leukotrienes after pulmonary anaphylaxis in the rat.
J Immunol. 1988 Nov 15; 141(10):3544-50.JI

Abstract

Inbred hyper-reactive rats, actively sensitized to OVA, were anesthetized, cannulated, and ventilated with room air. Tracheal instillation of Ag (OVA) resulted in an elevation of airways pressure (14.4 +/- 0.6 cm H2O). Measurement of biliary peptide leukotriene levels before and after Ag challenge using reverse phase HPLC and RIA techniques showed significant elevations in leukotriene (LT) levels, the amounts released being LTC4 (3.65 +/- 0.78), LTD4 (2.8 +/- 1.11), and N-Ac LTE4 (3.87 +/- 1.15) expressed as ng/100 g of body weight, n = 13. Identification of these metabolites were confirmed by HPLC/RIA techniques and LTC4 was further characterized by UV spectroscopy and its enzymatic conversion by gamma-glutamyl transpeptidase to LTD4. [3H]LTC4 (16 ng) administration by tracheal instillation resulted in a 31.4 +/- 4.3% recovery of radioactivity through the bile over 4 h (n = 3) with the major identified metabolite being N-Ac LTE4. [3H]LTC4 (16 ng) plus synthetic LTC4 (5 micrograms) showed a 30.8 +/- 3.1% recovery through the bile after tracheal instillation (3-h collection, n = 4) with significant amounts of LTC4 as well as N-Ac LTE4 present. [3H]LTC4 administration by the portal vein resulted in a 37.4 +/- 8.8% biliary recovery over 60 min (n = 6), the metabolites present in the bile being LTC4, LTD4, LTE4, and N-Ac LTE4. Pretreatment with the 5-lipoxygenase inhibitor L-656,224 (15 mg/kg, 3.5 h pre-p.o.) before Ag challenge resulted in a significant inhibition (greater than 90%, p less than 0.05) of biliary leukotriene levels in this model. Our study demonstrates that peptide leukotrienes are produced in the anesthetized rat after pulmonary anaphylaxis and that biliary leukotriene measurement is suitable for showing the biochemical efficacy of leukotriene inhibitors in vivo. In vivo tracer experiments suggest that the biliary metabolic profile of the peptide leukotrienes is dependent on the site and levels of release as well as the efficiency of the vascular clearance of the various metabolites.

Authors+Show Affiliations

Department of Pharmacology, Merck Frosst Canada Inc., Pointe Claire-Dorval, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2846689

Citation

Foster, A, et al. "The in Vivo Production of Peptide Leukotrienes After Pulmonary Anaphylaxis in the Rat." Journal of Immunology (Baltimore, Md. : 1950), vol. 141, no. 10, 1988, pp. 3544-50.
Foster A, Letts G, Charleson S, et al. The in vivo production of peptide leukotrienes after pulmonary anaphylaxis in the rat. J Immunol. 1988;141(10):3544-50.
Foster, A., Letts, G., Charleson, S., Fitzsimmons, B., Blacklock, B., & Rokach, J. (1988). The in vivo production of peptide leukotrienes after pulmonary anaphylaxis in the rat. Journal of Immunology (Baltimore, Md. : 1950), 141(10), 3544-50.
Foster A, et al. The in Vivo Production of Peptide Leukotrienes After Pulmonary Anaphylaxis in the Rat. J Immunol. 1988 Nov 15;141(10):3544-50. PubMed PMID: 2846689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The in vivo production of peptide leukotrienes after pulmonary anaphylaxis in the rat. AU - Foster,A, AU - Letts,G, AU - Charleson,S, AU - Fitzsimmons,B, AU - Blacklock,B, AU - Rokach,J, PY - 1988/11/15/pubmed PY - 1988/11/15/medline PY - 1988/11/15/entrez SP - 3544 EP - 50 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 141 IS - 10 N2 - Inbred hyper-reactive rats, actively sensitized to OVA, were anesthetized, cannulated, and ventilated with room air. Tracheal instillation of Ag (OVA) resulted in an elevation of airways pressure (14.4 +/- 0.6 cm H2O). Measurement of biliary peptide leukotriene levels before and after Ag challenge using reverse phase HPLC and RIA techniques showed significant elevations in leukotriene (LT) levels, the amounts released being LTC4 (3.65 +/- 0.78), LTD4 (2.8 +/- 1.11), and N-Ac LTE4 (3.87 +/- 1.15) expressed as ng/100 g of body weight, n = 13. Identification of these metabolites were confirmed by HPLC/RIA techniques and LTC4 was further characterized by UV spectroscopy and its enzymatic conversion by gamma-glutamyl transpeptidase to LTD4. [3H]LTC4 (16 ng) administration by tracheal instillation resulted in a 31.4 +/- 4.3% recovery of radioactivity through the bile over 4 h (n = 3) with the major identified metabolite being N-Ac LTE4. [3H]LTC4 (16 ng) plus synthetic LTC4 (5 micrograms) showed a 30.8 +/- 3.1% recovery through the bile after tracheal instillation (3-h collection, n = 4) with significant amounts of LTC4 as well as N-Ac LTE4 present. [3H]LTC4 administration by the portal vein resulted in a 37.4 +/- 8.8% biliary recovery over 60 min (n = 6), the metabolites present in the bile being LTC4, LTD4, LTE4, and N-Ac LTE4. Pretreatment with the 5-lipoxygenase inhibitor L-656,224 (15 mg/kg, 3.5 h pre-p.o.) before Ag challenge resulted in a significant inhibition (greater than 90%, p less than 0.05) of biliary leukotriene levels in this model. Our study demonstrates that peptide leukotrienes are produced in the anesthetized rat after pulmonary anaphylaxis and that biliary leukotriene measurement is suitable for showing the biochemical efficacy of leukotriene inhibitors in vivo. In vivo tracer experiments suggest that the biliary metabolic profile of the peptide leukotrienes is dependent on the site and levels of release as well as the efficiency of the vascular clearance of the various metabolites. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/2846689/The_in_vivo_production_of_peptide_leukotrienes_after_pulmonary_anaphylaxis_in_the_rat_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=2846689 DB - PRIME DP - Unbound Medicine ER -