The Possible Role of Substance P in the Allergic Reaction, Based on Two Different Provocation Models

Nieber, K; Baumgarten, C; Witzel, A.; Rathsack, R; Oehme, P; Brunnée, T.; Kleine-Tebbe, J.; Kunkel, G.

doi:10.1159/000235397

Cited by 43 publications

(17 citation statements)

References 13 publications

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“…Recent studies have shown that local ap plication of SP enhances nasal secretion in humans [10] and also increases the nasal challenge response to antigen [ 11 ]. It is likely that VIP also plays an important role in allergic and nonallergic nasal disease, since VIP alters glandular secretion by augment ing the flow of electrolytes and fluid from salivary glands [12], In human nasal secre tion, VIP is present in small amounts (0-50 pmol/1) [ 13].…”

Section: Introductionmentioning

confidence: 99%

Presence of Vasoactive Intestinal Peptide Receptors in Nasal Mucosa

Agha-Mir-Salim

Baumgarten

Jahnke³

et al. 1991

Skin Pharmacol Physiol

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In recent years several tachykinins have been identified in the airway sensory nerves. Since the physiological and pathophysiological effects of neuropeptides depend on their functionally relevant concentrations and presence of specific receptors in the target tissue, specimens of enlarged turbinates and nasal polyps were removed in 11 patients and examined for the presence of vasoactive intestinal peptide (VIP) receptors. An intensive color reaction was observed in the cytoplasm of the tubular mucosa cells in polyps and turbinates as well as in the epithelium and submucosal glands. Since both these tissues reacted with VIP receptor antibody, noncross-reacting antibody against dendritic reticular cells (DRC 6-B7), nonspecific binding is possible, however it also must be speculated that the unspecific binding is overlaying specific binding. In addition a large number of cells located diffusely or in close association in the subepithelium and interstitial tissue stained only with VIP-specific antibody, indicating specific receptor binding. The color reaction is limited to the cell membrane and the cytoplasm of these cells was clearly eosinophilic. These cells were located in close proximity of the blood vessels, very indicative for active migration. Since VIP-positive nerves are also located near the blood vessels an activation process of these cells with subsequent release of enzymes and other active proteins is possible, thus influencing the inflammatory response.

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Section: Introductionmentioning

confidence: 99%

Presence of Vasoactive Intestinal Peptide Receptors in Nasal Mucosa

Agha-Mir-Salim

Baumgarten

Jahnke³

et al. 1991

Skin Pharmacol Physiol

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“…may induce a release of tachykinin-like substances in tracheal preparations from sensitized guinea pigs. A finding of an increased amount of substance P in bronchoalveolar fluid after bronchial allergen challenge in humans [38] indicates a similar scenario in the airways of asthmatics.…”

Section: Discussionmentioning

confidence: 85%

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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“…Furthermore, in the regulation of these mechanisms the neutral endopeptidase probably plays a key role. The recent finding of the increased amount of substance P in bronchoalveolar lavage fluid af ter bronchial allergen provocation in humans [35] is in fa vor of the similar scenario in the airways of asthmatics.…”

Section: Discussionmentioning

confidence: 92%

Inhibition of Neutral Endopeptidase Augments Anaphylactic Constriction of Guinea Pig Tracheal Smooth Muscle

Tudorić¹,

Coon²,

Flynn³

et al. 1993

Int Arch Allergy Immunol

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To determine whether tachykinins participate in antigen-induced constriction of tracheal smooth muscle, we examined the effects of a neutral endopeptidase inhibitor, phosphoramidon, the tachykinin antagonist (D-Pro⁴, D-Trp^7,9,10)-substance P(4-11), and capsaicin-induced tachykinin depletion on the responses to antigen in tracheal rings from ovalbumin-sensitized guinea pigs. In these preparations, the antigen (ovalbumin, 0.1 μg/ml) produced reproducible and durable constriction of tracheal smooth muscle. Incubation with phosphoramidon (10 min, 10 μM) prior to antigen challenge significantly augmented the magnitude of ovalbumin-induced constriction by 22% after 30 min and by 31% after 45 min. The addition of phosphoramidon at the plateau level of antigen-induced constriction produced a similar, significant increase in the magnitude of the constriction. Following incubation with tachykinin antagonist (D-Pro⁴, D-Trp^7,9,10)-substance P(4-11) (5 μM), the contractile response of the tracheal rings to the antigen was not altered. Furthermore, the addition of phosphoramidon (10 μM) did not significantly affect this contraction. Similarly, neither tachykinin antagonist nor phosphoramidon altered the ovalbumin-induced constriction of the tracheal rings from capsaicin-treated guinea pigs. Based on these findings, we hypothesize that tachykinins or similar broncho-constricting neutral endopeptidase substrates were released from tachykinin-containing nerve endings during immediate hypersensitivity reaction in airways, manifesting a modest and delayed constrictive effect. Following alteration of endopeptidase activity, these substances could modulate the anaphylactic constriction of the airway smooth muscle.

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The Possible Role of Substance P in the Allergic Reaction, Based on Two Different Provocation Models

Cited by 43 publications

References 13 publications

Presence of Vasoactive Intestinal Peptide Receptors in Nasal Mucosa

Presence of Vasoactive Intestinal Peptide Receptors in Nasal Mucosa

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

Inhibition of Neutral Endopeptidase Augments Anaphylactic Constriction of Guinea Pig Tracheal Smooth Muscle

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