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Peptidoleukotriene (PLT) Release and Absorption from the Airways of the Isolated Perfused Guinea Pig Lung Following Chemical and Antigenic Challenge

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Abstract

Purpose. To study the release and absorption of peptidoleukotrienes (PLTs) from the airways of the guinea pig lung following calcium ionophore A23187 (CI), benzalkonium chloride (BAC), ethylene diamine tetra-acetic acid (EDTA) or ovalbumin (OA) challenge.

Methods. PLT C4/D4/E4 were quantified in the perfusate of the isolated perfused guinea pig lung (IPGPL) following intratracheal administration of CI, BAC, EDTA or OA in different doses. The formation and airway-to-perfusate transfer kinetics of PLTs were analyzed by fitting mean data for cumulative PLT in perfusate vs. time to an A → B → C first-order release and transfer model, with dose-dependent transfer rate constants.

Results. CI induced apparent first order release of PLTs with a t\(\frac{1}{2}\) ≃ 1.2 minutes. The amount of PLT released was CI dose-dependent, as was the airway-to-perfusate transfer rate constant. These reached maxima of 0.254 μg and 0.0557 min.−1, respectively, around a CI dose of 100 μg. In OA-sensitized IPGPL preparations, OA induced a similar dose-dependent release of PLTs, although the rates of PLT release were much greater and more variable than those seen with CI. In OA sensitized IPGPL preparations, at an OA dose of 1000 μg, the maximum amount of PLT released was 0.289 μg and the maximal airway-to-perfusate transfer rate constant was 0.0229 min−1. BAC and EDTA failed to induce quantifiable PLT release from the airways.

Conclusions. Rapid release of the inflammatory mediators, PLT C4/ D4/E4, could be induced in the unsensitized IPGPL by CI, and in the sensitized IPGPL by OA. Transfer into perfusate occurred in both cases with dose-dependent t\(\frac{1}{2}\) ranging from 12.4 through 57.8 minutes.

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  1. Aerosol Research Group, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, 23298

    Rosemary A. Kovelesky, Peter R. Byron & Jürgen Venitz

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  1. Rosemary A. Kovelesky
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  2. Peter R. Byron
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Correspondence to Peter R. Byron.

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Kovelesky, R.A., Byron, P.R. & Venitz, J. Peptidoleukotriene (PLT) Release and Absorption from the Airways of the Isolated Perfused Guinea Pig Lung Following Chemical and Antigenic Challenge. Pharm Res 16, 321–326 (1999). https://doi.org/10.1023/A:1018801113797

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