Characterization of contractile prostanoid receptors on human airway smooth muscle

https://doi.org/10.1016/0014-2999(89)90715-2Get rights and content

Abstract

In human bronchial rings the thromboxane A2 (TxA2) mimetic, U46619, produced cumulative concentration-related contractions up to a maximum of 141 ± 23% of the response induced by carbachol or acetylcholine. The geometric were EC50 value was 3.2 × 10−8 M (95% confidence interval: 1.2, 8.9 × 10−8 M) (n = 5). Contractions to U46619 were unaffected by atropine (10−6 M) or verapamil (10−5 M), but were competitively antagonized by the TxA2 antagonist GR32191 with a pA2 value of 8.40 ± 0.41. The maximum contractile response to prostaglandin (PG) F was smaller (90 ± 9%, n = 13) and the potency was less (EC50 = 2 × 10−6M) than that of U46619. Contractions to PGF were also competitively antagonized by GR32191 with a pA2 value of 8.18 ± 0.08. Concentration-response curves to PGE2 were biphasic, relaxation at concentrations from 10−9 to 10−6 M and contraction from 10−6 to 3 × 10−5 M. GR32191 10−7 M inhibited the contractile portion of the response curve in 8 of 11 tissues. Based on these results we conclude that U46619, PGF and PGE2 all contract human airways by stimulation of the TxA2 (TP) receptor.

References (26)

  • O. Arunlakshana et al.

    Some quantitative uses of drug antagonists

    Br. J. Pharmacol.

    (1959)
  • C. Brink et al.

    The interaction between indomethacin and contractile agents on human isolated airway muscle

    Br. J. Pharmacol.

    (1980)
  • J.L. Black et al.

    Receptor mechanisms for 5-hydroxytryptamine in rabbit arteries

    Br. J. Pharmacol.

    (1981)
  • Cited by (58)

    • Sex steroids effects on guinea pig airway smooth muscle tone and intracellular Ca<sup>2+</sup> basal levels

      2017, Molecular and Cellular Endocrinology
      Citation Excerpt :

      It is well known that among all prostanoids, the main three that can be produced in airway smooth muscle and have an effect on this tissue are: thromboxane A2 (TXA2), prostaglandin F2α (PGF2α) and PGE2. Regarding TXA2 and PGF2α, it was reported (Armour et al., 1989) that they induce airway smooth muscle contraction through the activation of a TP receptor. Later on, it was stated that these prostanoids also augmented intracellular Ca2+ concentrations (Shiraki et al., 2009; Takata et al., 1999).

    • Lipid Mediators and Lung Function

      2015, Comparative Biology of the Normal Lung: Second Edition
    • Modulation of antigen-induced responses by serotonin and prostaglandin E<inf>2</inf> via EP<inf>1</inf> and EP<inf>4</inf> receptors in the peripheral rat lung

      2013, European Journal of Pharmacology
      Citation Excerpt :

      TXA2 may also cause airway hyperresponsiveness (Held and Uhlig, 2000) and contributes to cytokine-induced bronchoconstriction (Martin et al., 2001). PGD2 is a pro-inflammatory mediator of allergic asthma (Matsuoka et al., 2000), a marker of mast cell activation (Dahlen and Kumlin, 2004) and induces airway and vascular smooth muscle contractions via the TP receptor (Armour et al., 1989; Beasley et al., 1989; Johnston et al., 1995; Larsson et al., 2011; McKenniff et al., 1991). PGE2 is implicated to have a beneficial role in the lung (Pavord and Tattersfield, 1995; Vancheri et al., 2004), since this prostanoid may maintain airway tone (Tilley et al., 2003) and attenuate allergic airway responses (Hartney et al., 2006; Martin et al., 2002).

    View all citing articles on Scopus
    View full text