Tachykinin control of ferret airways: Mucus secretion, bronchoconstriction and receptor mapping

Meini, Stefania; Mak, Judith C.W.; Rohde, J. A. L.; Rogers, Duncan F.

doi:10.1016/0143-4179(93)90025-6

Cited by 34 publications

(33 citation statements)

References 20 publications

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“…Tissues were stimulated at 10 Hz, 50 V and 0.5 ms for the first 5 min of a 15min collection period. We have previously established optimal conditions under which collections are taken in order to define baseline secretion and to maximize detection of the secretory response to drug addition (Meini et al, 1993). At time Oh, Na235SO4 (0.1 mCi; Amersham International plc, Aylesbury, Bucks.)…”

Section: Methodsmentioning

confidence: 99%

“…To examine the effects of antagonists on baseline and stimulated secretion, drugs were added to the luminal half chambers for varying times before stimulation: atropine, phentolamine and propranolol (APP) (Meini et al, 1993). In the present study we determined whether there was tachyphylaxis between consecutive electrical stimulations.…”

Section: Protocols For Secretory Studiesmentioning

confidence: 99%

“…The order of potency of the natural tachykinins (i.e. SP > NKA > NKB: Lundgren et al, 1989;Mizoguchi & Hicks, 1989;Webber, 1989;Gentry, 1991), and of synthetic agonists selective for the three classes of tachykinin receptor (Geppetti et al, 1993;Meini et al, 1993) in inducing mucus secretion indicate that tachykinin NK1 receptors mediate tachykinin-induced secretion. However, the relevance of tachykinins to control of mucus secretion induced by stimulation of sensory-efferent nerves and the tachykinin receptor(s) involved in the response is not reported.…”

Section: Introductionmentioning

confidence: 99%

“…We used the selective NKI receptor antagonists, FK888 Hirayama et al, 1993) andL-668,169 (McKnight et al, 1988;Williams et al, 1988), the NK2 receptor antagonist SR 48968 (Advenier et al, 1992a,b;Edmonds-Alt et al, 1992;Martin et al, 1992), and the dual NKI/NK2 receptor antagonist FK224 Murai et al, 1992;Hirayama et al, 1993). We used the ferret trachea to study sensory-efferent neural control of mucus secretion because: (a) mucus secretion can be induced in this preparation via NANC neural mechanisms (Borson et al, 1984); (b) the source of mucus is identifiable because the trachea of this species contains abundant submucosal glands and very few epithelial goblet cells (Robinson et al, 1986;Meini et al, 1993); (c) the ferret trachea is supplied by axons containing sensory neuropeptides (Luts & Sundler, 1989); and (d) the airway submucosal glands express SP receptors (Meini et al, 1993). We used 3sSO4 as the mucus label, because it is a marker predominately for tracheal submucosal gland mucous glycoprotein in the ferret (Gashi et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

“…The selectivity of FK888 and SR 48968 in the ferret was investigated by determining their activity on NKA-induced tracheal smooth muscle contraction in vitro, a preparation which synthetic agonists indicate as essentially an NK2 receptor system (Geppetti et al, 1993;Meini et al, 1993). The selectivity of SR 48968 was further investigated against secretion induced by [Sar9Met(02)"] substance P ([Sarl), a synthetic agonist selective for the NK1 receptor (Maggi et al, 1990) which induces secretion in the ferret trachea (Meini et al, 1993). Some of these results have been published in abstract form (Ramnarine et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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‘Sensory‐efferent’ neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro

Ramnarine

Hirayama

Barnes

et al. 1994

British J Pharmacology

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1 We characterized the tachykinin receptor(s) mediating 'sensory-efferent' neural control of release of 35SO4-labelled macromolecules (mucus) from ferret trachea in vitro in Ussing chambers using selective tachykinin antagonists. Secretion was induced by substance P (SP), neurokinin A (NKA), capsaicin, the NK, tachykinin receptor agonist [Sar9, Met (02) inhibited SP-induced secretion in a dose-dependent manner, with complete inhibition at 1OIM and an ICso of 1 fLM. L-668,169 (1 ELM) also completely inhibited SP-induced secretion.3 NKA (1 pLM) significantly increased mucus secretion by 271% above baseline, a response which was completely inhibited by FK888 (10tiM) or L-668,169 (ftM). Secretion induced by ACh (10tiM: 317% above baseline) was not inhibited by FK888 but was inhibited by atropine. Capsaicin (10 tM)-induced secretion (456% above vehicle controls) was significantly inhibited by FK888 and by L-668,169 (111% and 103% inhibition respectively). 4 Electrical stimulation (50 V, 10 Hz, 0.5 ms, 5 min) increased mucus output above baseline (increased by 12 to 26 fold), a response blocked by tetrodotoxin (0.1 AM). FK888 (10 AM) inhibited the increase in secretion due to electrical stimulation by 47%. Atropine, propranolol and phentolamine in combination (APP) inhibited the response to electrical stimulation by 48%. The remaining NANC response, i.e. in the presence of APP, was further reduced by 66% with FK888. FK224 (10 JiM) inhibited neurallyevoked secretion by 73%. SR 48968 (0.1 fLM) had no effect on electrically-stimulated or [SarlSP-induced secretion. 5NKA (10nM-1O iLM: in the presence of DMSO control vehicle) induced tracheal smooth muscle contraction in a concentration-dependent manner with a maximal contraction of 30% of the maximal response to ACh (10 mM) and an ECm of 0.3 JAM. SR 48968 (0.1 JiM in DMSO) inhibited the NKAinduced contraction whereas FK888 did not. Neither antagonist had any inhibitory effect on AChinduced contraction. 6 We conclude that 'sensory-efferent' neurogenic mucus secretion in ferret trachea in vitro is mediated via tachykinin NK, receptors with no involvement of NK2 receptors. Potent and selective tachykinin antagonists may have therapeutic potential in bronchial diseases such as asthma and chronic bronchitis in which neurogenic mucus hypersecretion may be aetiologically important.

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Section: Methodsmentioning

confidence: 99%

Section: Protocols For Secretory Studiesmentioning

confidence: 99%