Antigen‐induced contraction of guinea‐pig isolated trachea: studies with novel inhibitors and antagonists of arachidonic acid metabolites

Jones, Thomas R.; Charette, L.; Denis, Danielle

doi:10.1111/j.1476-5381.1988.tb16578.x

Cited by 20 publications

(10 citation statements)

References 28 publications

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“…After addition of indomethacin to inhibit cyclo-oxygenase activity, the tracheal tone was reduced and OA-induced contraction potentiated, as already reported (Brink et al, 1981;Jones et al, 1988;Braunstein et al, 1988). In these conditions, GABA was not effective.…”

Section: Discussionsupporting

confidence: 56%

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GABA‐mediated inhibition of the anaphylactic response in the guinea‐pig trachea

Gentilini

Franchi‐Micheli

Mugnai

et al. 1995

British J Pharmacology

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In sensitized guinea‐pigs, the effects of γ‐aminobutyric acid (GABA) and GABAmimetic drugs have been investigated on tracheal segments contracted by cumulative application of an allergen (ovoalbumin, OA) and on serosal mast cells. The same drugs have also been tested on activation of alveolar macrophages isolated from unsensitized guinea‐pigs. Superfusion with GABA (1–1000 μM) reduced the contraction intensity of tracheal strips. The effect of GABA (100 μM) was not affected by the carrier blockers, nipecotic acid and β‐alanine (300 μM each). It was mimicked by the GABAB agonist (−)−baclofen (100 μM) but not 3‐aminopropanephosphinic acid (100 μM, 3‐APA). The GABAA agonist, isoguvacine (100 μM) did not exert any effect. GABA (10 μM)‐induced inhibition of tracheal contractions was reduced by the GABAB antagonist, 2‐hydroxysaclofen (100 μM, 2‐HS), but not by the GABAA antagonist, bicuculline (30 μM). The reduction in contraction intensity induced by GABA (100 μM) was prevented by a 40 min preincubation of tracheal strips with capsaicin (10 μM), but not tetrodotoxin (TTX, 0.3 μM). The effect of GABA (1000 μM) was absent after preincubation with indomethacin (2.8 μM) but unmodified when nordihydroguaiaretic acid (NDGA, 3.3 μM) was used. Finally, removal of the epithelium prevented the GABA effect. Anaphylactic histamine release from serosal mast cells isolated from sensitized animals was not affected either by GABA (10–1000 μM) or the selective receptor agonists (−)−baclofen (0.1–1000 μM) and isoguvacine (10–1000 μM). The release of platelet‐activating factor (PAF) from alveolar macrophages stimulated by formyl‐Met‐Leu‐Phe (FMLP; 1 μM) was modified neither by GABA (100 μM) nor by (−)−baclofen (100 μM). In conclusion, these data show that GABA can inhibit allergic phenomena in the guinea‐pig airways through activation of GABAB receptors. An involvement of neuropeptidergic sensory structures is suggested but a role for epithelial cells and arachidonate metabolites is not definitely proved.

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Section: Discussionsupporting

confidence: 56%

“…From these data the involvement of an endogenous prostanoid in the action of GABA could be proposed. Other explanations cannot be ruled out in view of the fact that indomethacin profoundly affected tracheal responsiveness (Brink et al, 1981;Jones et al, 1988;Braunstein et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

GABA‐mediated inhibition of the anaphylactic response in the guinea‐pig trachea

Gentilini

Franchi‐Micheli

Mugnai

et al. 1995

British J Pharmacology

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“…However, in this study the guinea pig tra cheal preparations were continuously incubated with indomethacin. Jones et al [20] demonstrated the potent inhibitory effect of AA-861 (10 and 30 pM) in tracheal preparations pretreated with indomethacin and mepyramine or atropine and mepyramine, whereas in the ab sence of these chemicals AA-861 was ineffective. Despite the significant differences in the experimental design, the cited studies suggest the important role of cyclooxygenase inhibition on the effects of AA-861.…”

Section: Resultsmentioning

confidence: 99%

Phosphoramidon Modulates Effects of the 5-Lipoxygenase Inhibition on Anaphylactic Contraction of the Guinea Pig Trachea

Tudorić

Coon²,

Bošnjak³

1994

Int Arch Allergy Immunol

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Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins increases anaphylactic contraction of guinea pig tracheal smooth muscle. It was suggested that anaphylactic release of tachykinin-like substances is likely to be responsible for the observed increases in tracheal contractions. To obtain additional information on the mechanisms responsible for anaphylactic release of tachykinins in guinea pig trachea, we examined the effects of phosphoramidon, an inhibitor of neutral endopeptidase, on contractile response to antigen after preincubation with the selective 5-lipoxygenase inhibitor AA-861. AA-861 (5 μM) significantly reduced ovalbumin-induced contraction, although the effect was not constant. A marked spontaneous increase in contraction was observed. Phosphoramidon (10 μM) produced significant increase of this contraction (27% after 30 min, and 33% after 45 min). The addition of H₁-histamine receptor antagonist (diphenhydramine HCl,10 μM) produced additional inhibition of the initial phase of antigen-induced contraction, while its later phase, apart from a spontaneous increment in magnitude, remained similar. Phosphoramidon (10 μM) increased the contraction by 26% after 30 min, and by 34% after 45 min. Since the effects of histamine and 5-lipoxygenase pathway products were prevented, we hypothesize that cyclooxygenase pathway products are responsible for the phosphoramidon-dependent increase in antigen-induced contraction. In accordance with previously reported ineffectiveness of contractile prostaglandins, we suggest that the relaxant prostaglandins are most important in mediating the release of tachykinins during the immediate hypersensitivity reaction in guinea pig trachea.

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“…We used a single dose of antigen (ovalbumin, 1 ¡.ig/ml), a concentration which consistently produced submaximal and reproduc ible responses [17,29] and released considerably large amounts of histamine and leukotrienes [30], the com pounds which are suggested as being the principal media tors of anaphylactic bronchoconstriction in guinea pig [28]. Based on the effects of antihistamines, several stud ies reported the role of histamine in the initial phase of the antigen-induced contraction [28.…”

Section: Discussionmentioning

confidence: 99%

Phosphoramidon Augments Contraction of Guinea Pig Tracheal Smooth Muscle Induced by Histamine and Leukotriene-D4

Tudorić¹,

Coon²,

Bošnjak³

1994

Int Arch Allergy Immunol

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Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. Anaphylactic release of tachykinin-like substances was indicated. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on contraction induced by mediators of anaphylaxis. Phosphoramidon significantly increased histamine- and leukotriene D4-induced contractions of tracheal rings from unsensitized animals (by 14 and 48%, respectively), but failed to alter the contractile responses to prostaglandins D2 and F2α. In tracheal rings preincubated with tachykinin antagonist-[D-Pro⁴, D-Trp^{7, 9}]-substance P(4-11), or in capsaicin-desensitized tracheal rings, phosphoramidon did not change histamine- and leukotriene D4-induced contractions. In the second part of the study, performed on tracheal rings obtained from ovalbumin-sensi-tized guinea pigs, we examined the effects of phosphoramidon on contractile responses to histamine and leukotrienes which are released after antigen challenge. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl) or leukotriene receptor antagonist (ICI 198.615) prevented a phosphoramidpn-dependent increase of antigen-induced contraction. These results indicate that histamine and leukotrienes may be involved in the anaphylactic release of tachykinin-like substances or other neutral endopeptidase substratum.

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Antigen‐induced contraction of guinea‐pig isolated trachea: studies with novel inhibitors and antagonists of arachidonic acid metabolites

Cited by 20 publications

References 28 publications

GABA‐mediated inhibition of the anaphylactic response in the guinea‐pig trachea

GABA‐mediated inhibition of the anaphylactic response in the guinea‐pig trachea

Phosphoramidon Modulates Effects of the 5-Lipoxygenase Inhibition on Anaphylactic Contraction of the Guinea Pig Trachea

Phosphoramidon Augments Contraction of Guinea Pig Tracheal Smooth Muscle Induced by Histamine and Leukotriene-D4

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