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Immunopharmacolgy - Essay Example

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Phosphoramidamon is the derivate of Streptomyces tanashiensis MD706-Y4 (see Fig. 1). There is known that phosphoramidon can inhibit thermolysins and endothelin converting enzyme (Zhang, Adner & Cardell, 2004) and, particularly, can inhibit neural endopeptidase (NEP24.11)…
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Download file to see previous pages The authors showed also that phosphoramidon significantly potentiates neuropeptide-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level (ibid, p. 945).
There are no available data about the combined action of posphoramidon and histamine and capscaicin. Nevertheless, some authors discuss the mechanisms of interaction between peptidergic and histaminergic stimuli in the pathogenesis of bronchial asthma (Crimi et al., 1995; O'Connor et al., 2004; Kirsch et al., 1992; Crimi et al., 1988). For example, the results of Intalian scientists (Crimi et al., 1995) provided evidence of phosphoramidon role in the mediation of Bradykinin-related responses but not in the mediation of histaminergic effects. Contrarily, capsaicin and phosphoramidon have synergistic effects on the bronchial tone (Sagara et al., 1993).
To determine whether the epithelium influenced the effect of endogenously released and exogenously released substance P on smooth muscle function there is expediently to conduct two different experiments. The first one will test the action of exogenously released substance P and can be conducted in vivo with the administration of substance P via inhalation. The effects of endogenously released substance P could be tested in the in vitro study with isolated tracheal ring where some of them will be processed by the airway epithelium removal.
The major effect of epithelium removal on the contractile response to substance P could be related to the loss of neutral endopeptidase and neuropeptide degradation. This hypothesis also is proved by the numerous experimental studies (Toews et al., 1997; Frossard et al., 1989 etc)
1. Crimi et al. (1988) Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects. Clin Allergy. 18(4) pp. 375-82
2. Crimi et al. (1995) Effect of an inhaled neutral endopeptidase inhibitor, phosphoramidon, on baseline airway calibre and bronchial responsiveness to bradykinin in asthma. 4Thorax. 50(5):505-10.
3. Gallelli et al. (2003) Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal instillation in the rabbit. Life Sci. 72(10) 1135-1142.
4. Kirsch et al. (1992) Mechanism of platelet activating factor-induced vascular leakage in the rat trachea. Exp Lung Res. 18(4) pp. 447-459.
5. 4Lotvall et al. (1991) Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig. Br J Pharmacol. 104(4):945-9.
6. Marini et al. (1996) Endothelin-1 induces increased fibronectin expression in human bronchial epithelial cells. Biochem Biophys Res Commun. 220(3) 896-899.
7. 4O'Connor et al. (2004) The role of substance P in inflammatory disease. J Cell Physiol. 201(2):167-80.
8. 4Sagara et al. (1993) Effect of capsaicin on the migration of eosinophils into the bronchi of guinea pigs Arerugi. 42(3 Pt 1):236-42
9. 4Toews, Ustinova & Schultz (1997) Lysophosphatidic acid enhances contractility of isolated airway smooth muscle. J Appl Physiol. 1997 Oct;83(4):1216-22.
10. 4Zhan, Adner & Cardell (2004) Interleukin-1beta attenuates endothelin B receptor-mediated airway contractions in a murine in vitro model of asthma: roles of endothelin converting enzyme and mitogen-activated protein kinase pathways. Clin Exp Allergy. 34(9) pp. ...Download file to see next pagesRead More
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