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Differential effects of phosphoramidon and captopril on NK1 receptor-mediated plasma extravasation in the rat trachea

  • Inflammation
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Abstract

We sought to confirm the identity of the tachykinin receptor subtype that mediates plasma extravasation in the rat trachea, and assess the respective contributions of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) in regulating this tachykinin-induced response. To achieve these aims, we determined the relative potencies of several natural tachykinins and receptor-selective synthetic agonists, both before and after inhibiting NEP with phosphoramidon and ACE with captopril. We also determined the effects of these peptidase inhibitors, and the NK-1 receptor antagonist L-703,606, on the plasma extravasation produced by capsaicin, which releases tachykinins endogenously from sensory nerve endings. We found that the rank order of potency for producing plasma extravasation in the rat trachea was NK-1 receptor agonist ([Sar9, Met(O2)11] SP)>substance P>neurokinin A> neurokinin B. The NK-2 ([Nle10]NKA (4–10)) and NK-3 ([MePhe7]NKB) receptor agonists were without effect. We observed no change in the relative potencies of these peptides after giving rats phosphoramidon or captopril, which suggests that the different peptide potencies are not simply the consequence of different rates of enzymatic degradation. Nevertheless, the responses to substance P and neurokinin A were clearly potentiated in rats given phosphoramidon, indicating that NEP effectively degrades tachykininsin vivo. No significant potentiation was evident for any peptide in rats given captopril. Similarly, the plasma extravasation produced by capsaicin was potentiated in rats given phosphoramidon, but not in those given captopril. Pretreating rats with L-703,606 abolished the response to capsaicin. We conclude from these observations that NK-1 receptors mediate tachykinin-induced plasma extravasation in the rat trachea, and that NEP regulates this response with little or no contribution from ACE.

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  1. Department of Anatomy, Indiana University School of Medicine, 1800 Lincoln Avenue, 47722, Evansville, Indiana, USA

    James J. Brokaw & Gary W. White

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  1. James J. Brokaw
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Brokaw, J.J., White, G.W. Differential effects of phosphoramidon and captopril on NK1 receptor-mediated plasma extravasation in the rat trachea. Agents and Actions 42, 34–39 (1994). https://doi.org/10.1007/BF02014297

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  • DOI: https://doi.org/10.1007/BF02014297

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