The Schultz-Dale reaction: A review

Chand, N.; Eyre, P.

doi:10.1007/bf01966600

Cited by 61 publications

(50 citation statements)

References 98 publications

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“…These results suggested that mast cell-derived renin triggers the local formation of ANG II, which then acts on AT 1 R on bronchial smooth muscle eliciting contraction. We then compared the bronchial contractile response to ANG II to that of methacholine, a prototypical bronchoconstricting agent [positive control (17,18)] and histamine, another bronchoconstricting agent (17), to which the rat is insensitive [negative control (19,20)]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Mast cell renin and a local renin–angiotensin system in the airway: Role in bronchoconstriction

Veerappan¹,

Reid²,

Estephan³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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We previously reported that mast cells express renin, the ratelimiting enzyme in the renin-angiotensin cascade. We have now assessed whether mast cell renin release triggers angiotensin formation in the airway. In isolated rat bronchial rings, mast cell degranulation released enzyme with angiotensin I-forming activity blocked by the selective renin inhibitor BILA2157. Local generation of angiotensin (ANG II) from mast cell renin elicited bronchial smooth muscle contraction mediated by ANG II type 1 receptors (AT 1R). In a guinea pig model of immediate type hypersensitivity, anaphylactic mast cell degranulation in bronchial rings resulted in ANG II-mediated constriction. As in rat bronchial rings, bronchoconstriction (BC) was inhibited by a renin inhibitor, an AT 1R blocker, and a mast cell stabilizer. Anaphylactic release of renin, histamine, and ␤-hexosaminidase from mast cells was confirmed in the effluent from isolated, perfused guinea pig lung. To relate the significance of this finding to humans, mast cells were isolated from macroscopically normal human lung waste tissue specimens. Sequence analysis of human lung mast cell RNA showed 100% homology between human lung mast cell renin and kidney renin between exons 1 and 10. Furthermore, the renin protein expressed in lung mast cells was enzymatically active. Our results demonstrate the existence of an airway renin-angiotensin system triggered by release of mast-cell renin. The data show that locally produced ANG II is a critical factor governing BC, opening the possibility for novel therapeutic targets in the management of airway disease.angiotensin II ͉ angiotensin II type 1 receptors ͉ asthma ͉ hypersensitivity ͉ lung T he renin-angiotensin system (RAS) has been traditionally viewed as a circulating axis, whereby renin is released into the circulation from the kidneys in response to decreased renal perfusion pressure, decreased delivery of NaCl at the macula densa, and/or increased renal sympathetic nerve activity (1). The proteolytic cleavage of angiotensinogen (aogen) by renin constitutes the rate-limiting step of the RAS cascade.In addition to this classical view, it is believed that many tissues, including the lung, may possess the capacity to generate angiotensin (ANG II) locally (2, 3). This is supported by experiments demonstrating that ANG II persists in lung of nephrectomized rats (4) and findings showing that ANG II can be elevated in the lungs in the absence of an elevated systemic RAS (5). Components of RAS have been identified in lung tissue, including aogen mRNA (6, 7), and angiotensin-converting enzyme (ACE), the pulmonary endothelium being the primary source for ACE in the body (8). ANG II receptors are also expressed in lung tissue, with the ANG II type 1 receptor (AT 1 R) subtype found on bronchial smooth muscle cells (9) and ANG II type 2 receptor (AT 2 R) observed on the bronchial epithelial cell brush border (10). An intrapulmonary source of renin protein has not yet been identified.We previously reported that mast cells synthesize, st...

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Section: Resultsmentioning

confidence: 99%

Mast cell renin and a local renin–angiotensin system in the airway: Role in bronchoconstriction

Veerappan¹,

Reid²,

Estephan³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…The Schultz-Dale reaction (Schultz, 1910;Dale, 1913;Chand & Eyre, 1978) has been used extensively to study anaphylactic contraction of airway tissue preparations such as the trachea, bronchi and lung parenchymal strips. Cumulative evidence showed that peptidoleukotrienes and histamine are the two major mast cell-derived mediators responsible for the anaphylactic contraction of the airways from both human and guinea-pig (Bjorck & Dahlen, 1993;Jonsson & Dahlen, 1994;Roquet et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Effects of mitogen‐activated protein kinase kinase inhibitor PD 098059 on antigen challenge of guinea‐pig airways in vitro

Tsang

Koh

Ting

et al. 1998

British J Pharmacology

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1 It has been shown that activation of protein tyrosine kinases is the earliest detectable signalling response to FceRI cross-linking on mast cell. Following tyrosine kinase activation, a family of mitogenactivated protein kinases (MAPKs) was found to be activated as well. The present study examined the role of MAPK signalling cascade in in vitro model of allergic asthma using a speci®c MAPK kinase inhibitor PD 098059. 2 Guinea-pigs were passively sensitized with IgG antibody raised against ovalbumin (OA). E ects of PD 098059 on OA-induced anaphylactic contraction of isolated bronchi and release of histamine and peptidoleukotrienes from chopped lung preparations were studied. 3 PD 098059 (10 ± 50 mM) produced only minor reduction of maximal OA-induced bronchial contraction. In contrast, the rate of relaxation of OA-induced bronchial contraction was markedly faster in the presence of PD 098059 than the vehicle control in a concentration-dependent manner. 4 These observations corroborate well with the inability of PD 098059 (5 ± 50 mM) to substantially block the OA-induced release of histamine and with marked inhibition of OA-induced release of peptidoleukotrienes from lung fragments in the presence of PD 098059. Exogenous arachidonic acidinduced release of peptidoleukotrienes from lung fragments was not blocked by PD 098059. 5 In immunoblotting study, we found that p42 MAPK was constitutively expressed in guinea-pig bronchi. However, treatment with OA, histamine or LTD 4 did not cause activation of p42 MAPK . These ®ndings together with the lack of inhibitory e ects of PD 098059 on bronchial contraction induced by histamine or LTD 4 suggest that histamine-and LTD 4 -induced bronchial contractions are not mediated by p42 MAPK activation. 6 Taken together, our ®ndings show that inhibition of MAPK signalling cascade by PD 098059 signi®cantly reduced the OA-triggered release of peptidoleukotrienes leading to rapid relaxation of anaphylactic bronchial contraction. On the other hand, p42 MAPK did not play a role in histamine-or LTD 4 -induced bronchial smooth muscle contraction suggesting that PD 098059 exerts its inhibitory e ects on OA-induced bronchial contraction primarily through inhibition of peptidoleukotrienes release from mast cells.

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“…Antigen-induced contraction of isolated trachealis from actively or passively sensitized guinea-pigs has been used by many investigators as a model of immediate hypersensitivity (Chand & Eyre, 1978;Adams & Lichtenstein, 1979;Hand & Buckner, 1979;Burka & Paterson, 1980;1981ab). Similarly, contraction to antigen can be elicited in passively (Dunlop & Smith, 1975;Dunlop et al, 1977;Adams & Lichtenstein, 1979;Davis et al, 1982) and intrinsically sensitized human tracheobronchial smooth muscle (Davis et al, 1982;Dahlen et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

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

Jones

Charette

Denis

1988

British J Pharmacology

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1 Responses of antigen-challenged isolated trachea from sensitized guinea-pigs were pharmacologically characterized by use of some novel inhibitors and antagonists of arachidonic acid metabolites. 2 The cyclo-oxygenase inhibitor, indomethacin, prolonged without altering the maximum response to antigen in the absence of the anti-muscarinic agent, atropine, and/or the Hl-receptor blocker, mepyramine. In the presence of mepyramine, indomethacin both prolonged and increased the magnitude of the response. The selective (SQ-29548) and non-selective (L-640,035) thromboxane A2 (TXA2)

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The Schultz-Dale reaction: A review

Cited by 61 publications

References 98 publications

Mast cell renin and a local renin–angiotensin system in the airway: Role in bronchoconstriction

Mast cell renin and a local renin–angiotensin system in the airway: Role in bronchoconstriction

Effects of mitogen‐activated protein kinase kinase inhibitor PD 098059 on antigen challenge of guinea‐pig airways in vitro

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

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