An ubiquitous modulating function of rabbit tracheal epithelium: degradation of tachykinins

Inoue, Kazuaki; Sakata, Yasushi; Homma, Ikuo

doi:10.1111/j.1476-5381.1992.tb14264.x

Cited by 14 publications

(4 citation statements)

References 26 publications

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“…The epithelium may also function as a metabolic barrier, reducing the amount of agonist reaching the smooth muscle layer via mechanisms such as the extraneural uptake of catecholamines (Farmer et al, 1986) or -5.0 -4.0 -3.0 -2.0 -1.0 through the effects enzymes such as neutral endopeptidase (Inoue et al, 1992) and acetylcholinesterase (Lev et al, log [ACh] 1990) that are localised in the epithelium. While the se response relationships to ACh from both correlation between epithelial loss and sensitivity to d bovine isovolumic bronchial segments.…”

Section: Discussionmentioning

confidence: 99%

“…Epithelial damage may lead to heightened responsiveness altering permeability of the epithelial layer (Holroyde, of airways by exposure of nerve endings (Barnes, 1987(Barnes, ), 1986Mitchell et al, 1990;Munakata et al, 1989; Small depletion of a putative epithelial derived relaxant factor et al Sparrow & Mitchell, 1991). (EpDRF) (Goldie et al, 1988Stuart-Smith & Animal models have shown that factors that alter Vanhoutte, 1988, Vanhoutte, 1988), uptake or degradaepithelial permeability, such as cigarette smoke, also tion of agonists (Farmer et al, 1986, Inoue et al, 1992 alter reactivity to inhaled agonists (Hogg, 1990; however have not supported these findings. O'Byrne et al (1984) showed that while asthmatics were 20-fold more sensitive to inhaled histamine, the permeability of their airways to 99mTc-DTPA (technetium-labelled diethylenetriamine pentacetic acid) was no different than that of control subjects.…”

Section: Introductionmentioning

confidence: 99%

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Responsiveness of human isolated bronchial segments and its relationship to epithelial loss.

Omari¹,

Sparrow²,

Mitchell³

1993

Brit J Clinical Pharma

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1. The responsiveness of human and bovine bronchi was examined by comparing the magnitude of responses to agonists applied to the adventitial (outside) and to the luminal (inside) surfaces. The development of smooth muscle tone was measured as both an increase in pressure in isovolumic bronchial segments and narrowing in perfused segments. 2. In both closed and perfused human segments, ACh added to the adventitial surface produced highly homogeneous responses while responses to ACh added to the luminal side were extremely variable. 3. Histological examination of the human segments showed that they possessed variable degrees of pre‐existing epithelial loss from the mucosal circumference, ranging from 0 to 82%. 4. Denuded human isovolumic segments (exhibiting > 30% epithelial loss) were 40 fold more sensitive to ACh inside than intact segments (< 30%). Denuded segments were also equally responsive to KCl inside or outside while KCl inside produced a contraction that was 50% of that to KCl outside in intact segments. 5. A strong and highly significant relationship was determined between the proportion of epithelial loss and both the responsiveness and rate of contraction of human segments to ACh and KCl introduced onto the lumen. No relationship was observed between epithelial denudation and responsiveness or contractility to agonists added to the adventitial surface. 6. Mechanical denudation of the epithelium from bovine segments had no effect on responsiveness to ACh or KCl added to the outside while significantly augmenting the sensitivity to ACh (9 fold) and reactivity to KCl introduced into the lumen to the extent that it became the same as outside.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Responsiveness of human isolated bronchial segments and its relationship to epithelial loss.

Omari¹,

Sparrow²,

Mitchell³

1993

Brit J Clinical Pharma

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“…The epithelium may act also as a metabolic barrier through the degradation or uptake of bioactive molecules as they pass through the cell. For example, the epithelial layer has been shown to alter the responsiveness of rabbit tracheal strips to substance P due to the presence of neutral endopeptidase (Inoue et al 1992). In addition, the epithelium has also been demonstrated to alter the responsiveness of airways to catecholamines via extra-neural uptake mechanisms (Farmer et al 1986).…”

Section: Discussionmentioning

confidence: 99%

Epithelial Disruption by Proteases Augments the Responsiveness of Porcine Bronchial Segments

Omari

Sparrow

1992

Clin Exp Pharma Physio

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1. The effect of disruption to the epithelium of intact porcine bronchi was examined by comparing the responsiveness to agonists applied to the adventitial and luminal surfaces. The development of smooth muscle tone was measured as an increase in pressure in an isovolumic bronchial segment of approximately 2 mm i.d. The reactivity and sensitivity to acetylcholine (ACh) introduced intraluminally was greatly attenuated when compared with adventitial addition. 2. Luminal exposure to K+ and vanadate (VO3-) had little effect compared with strong responses obtained by adventitial application. 3. Intraluminal exposure to trypsin, chymotrypsin and elastase (1 mg/mL) selectively augmented both the sensitivity and the reactivity to the luminal addition of ACh, K+ and carbachol. 4. Mechanical removal of the epithelium produced a 716-fold increase in sensitivity to ACh introduced luminally but had no effect on ACh applied adventitially. 5. The inhibitory effects of luminally introduced isoprenaline on electrical field stimulation responses were also significantly potentiated in segments stripped of epithelium. 6. The evidence presented here indicates that the responsiveness of in vitro airways segments is highly influenced by the epithelial layer, which acts most prominently as a barrier inhibiting the penetration of luminally introduced agonists.

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“…5), rather than the total amount, is critical to its function. Epithelial NEP activity is important in modulating contractile responses of airways to SP [18,19]; removal of the epithelium from 16-20 week old Japanese white rabbit tracheas enhanced contractile responses to SP; however, no difference was seen in the contractile response to SP between intact and epithelium-denuded preparations in the presence of a NEP inhibitor [19]. COLASURDO et al [18], in a preliminary report, showed that epithelial removal increased responses of tracheal rings to SP in 1 week old rabbits, but not in adults.…”

Section: Discussionmentioning

confidence: 99%

Neutral endopeptidase activity in newborn and adult rabbit tracheas

Haver

Gérard²,

Kobzik³

et al. 1997

Eur Respir J

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Neutral endopeptidase (NEP, E.C. 3.4.24.11), a widely distributed ectoenzyme, cleaves and inactivates a variety of biologically active peptides, including the tachykinin, substance P (SP). This study was undertaken to determine whether the modulation of SP airway smooth muscle contraction by NEP is agedependent.We studied the contractile response of isolated tracheal rings from newborn and 120 day old New Zealand white rabbits. We measured NEP activity and determined immunoreactive NEP content in tracheal membrane preparations. NEP activity was then localized histochemically in sections of rabbit tracheas.In the presence of the NEP inhibitor, SCH 32615, the contractile response of isolated tracheal rings to SP was increased both in the newborn and 120 day old rabbits. However, the increase was greatest in the newborn animals. NEP activity in tracheal membrane preparations increased fivefold between the newborn and 120 day old rabbits. Western blot analysis also revealed a significant increase in the immunoreactive NEP content of these tracheal membrane preparations between the newborn and 120 day old rabbits. NEP activity, localized histochemically, was most intense in the epithelial region of the newborn animals, with a shift of activity to the subepithelial region with age.The prominent epithelial localization of neutral endopeptidase in the tracheas of these 1 day old rabbits, which we have shown to have relatively low neutral endopeptidase activity, suggests that the location of neutral endopeptidase in the airway, including proximity to relevant substance P receptors, may be critical to its function.

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An ubiquitous modulating function of rabbit tracheal epithelium: degradation of tachykinins

Cited by 14 publications

References 26 publications

Responsiveness of human isolated bronchial segments and its relationship to epithelial loss.

Responsiveness of human isolated bronchial segments and its relationship to epithelial loss.

Epithelial Disruption by Proteases Augments the Responsiveness of Porcine Bronchial Segments

Neutral endopeptidase activity in newborn and adult rabbit tracheas

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