Effects of endothelin-1 on tracheal submucosal gland secretion and epithelial function in the ferret.
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Albumins↗
Biomedical subjects
S E Webber
Publications and source records attributed to S E Webber.
The actions of bradykinin and lys-bradykinin on tracheal blood flow and smooth muscle in anaesthetized sheep.
The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin -52.8% (46.5-59.1%). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (greater than 1.9 pmoles) of both kinins. Intravenous indomethacin (5 mg.kg-1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 microns at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.
Anesthesia↗
The effect of hydrogen peroxide on smooth muscle tone, mucus secretion and epithelial albumin transport of the ferret trachea in vitro.
The effect of hydrogen peroxide (H2O2) was examined on baseline and on methacholine- and phenylephrine-stimulated smooth muscle tone, mucus volume and lysozyme outputs, and epithelial albumin transport of the ferret whole trachea in vitro. H2O2 (10 microM-10 mM) had no significant effect on tracheal smooth muscle tone but produced concentration-dependent increases in mucus volume, lysozyme and albumin outputs. The potential difference (P.D.) across the trachea was not changed by H2O2. Exposure of the trachea to H2O2 (1 mM) for 2 h reduced the smooth muscle contractions and lysozyme outputs due to methacholine (1 microM) and phenylephrine (10 microM). Methacholine-induced albumin output was significantly increased by H2O2 but that due to phenylephrine was not significantly affected. Exposure to H2O2 had no significant effect on the mucus volume output produced by methacholine or phenylephrine. Thus H2O2 directly stimulates submucosal gland secretion, including secretion from serous cells, and epithelial albumin transport across the ferret trachea but has no effect on tracheal smooth muscle tone. H2O2 reduces methacholine- and phenylephrine-induced smooth muscle contractions and serous cell secretion. H2O2 causes hyperresponsiveness of albumin output to methacholine but not to phenylephrine.
Animals↗
Mechanisms of platelet activating factor-induced changes in sheep tracheal blood flow.
1. The effects of platelet activating factor (PAF) have been studied on the cervical tracheal vasculature and smooth muscle of anaesthetized sheep. 2. The predominant action of PAF (2 pmol-2nmol) was a dose-dependent fall in tracheal vascular resistance. The maximum fall in resistance was -41.6% (-38.5 to -44.7%, 95% confidence interval) and the ED50 was 17 pmol (12-28 pmol). Lyso-PAF (200 pmol) did not change vascular resistance. 3. PAF had no effect on tracheal smooth muscle tone assessed by measuring changes in the external diameter of the trachea. 4. The fall in vascular resistance produced with PAF was unaffected by the anti-asthma drug nedocromil sodium (1 mg, i.a.), the cyclo-oxygenase inhibitor indomethacin (5 mg kg-1, i.v.), the leukotriene receptor antagonist FPL55712 (2 mg kg-1, i.v.), or a combination of the histamine H1- and H2-antagonists mepyramine (2 mg kg-1, i.v.) with cimetidine (5 mg kg-1, i.v.). The PAF antagonist WEB 2086 (300 micrograms kg-1, i.v.) significantly reduced the vasodilatation produced by PAF (before, -40.8 +/- 4.2%; after -16.5 +/- 5.9%, P less than 0.05). 5. Thus in this model, PAF is a potent vasodilator of the tracheal circulation but has no action on tracheal smooth muscle. The vasodilatation is mediated by specific PAF receptors and is not due to the release of prostanoids, leukotrienes or histamine.
Animals↗
The effects of calcitonin gene-related peptide on submucosal gland secretion and epithelial albumin transport in the ferret trachea in vitro.
1. We have examined the effect of calcitonin gene-related peptide (CGRP) on basal mucus volume, lysozyme and albumin outputs from the ferret whole trachea in vitro, and on the outputs produced by methacholine and substance P (SP). We have also examined the effect of inhibiting neutral enkephalinase with thiorphan on the responses to CGRP. 2. CGRP (1-100 nM) produced small concentration-dependent increases in basal mucus volume, lysozyme and albumin outputs. These effect of CGRP were enhanced by thiorphan. The increases in basal outputs with CGRP and the potentiation by thiorphan were considerably less than previously observed with SP and neurokinin A (NKA). CGRP had no significant effect on potential difference (PD) across the trachea. 3. CGRP produced a concentration-dependent inhibition of methacholine- and SP-induced lysozyme output but a concentration-dependent increase in methacholine- and SP-induced albumin output. The effects of CGRP on methacholine-induced lysozyme and albumin outputs were enhanced by thiorphan. CGRP weakly inhibited methacholine-induced mucus volume output and weakly enhanced SP-induced mucus volume output. 4. Thus, CGRP weakly stimulates basal serous cell secretion and epithelial albumin transport, but does not alter epithelial integrity. CGRP inhibits the serous cell secretion due to methacholine or SP, but potentiates the epithelial albumin transport produced by these agents. The interaction between CGRP and other sensory neuropeptides or muscarinic agonists on airway submucosal glands and epithelium may be important in the normal airway and in inflammatory airway diseases where release of sensory neuropeptides is enhanced.
Albumins↗
Endothelin-1 inhibits pre-stimulated tracheal submucosal gland secretion and epithelial albumin transport.
1. Endothelin-1 potently contracts smooth muscle, including that in the airways. However, its effect on airway mucosal function has not so far been studied. 2. We have used the ferret whole trachea in vitro to examine the effect of endothelin-1 on tracheal smooth muscle tone, transepithelial potential difference (p.d.), submucosal gland secretion (including lysozyme secretion from serous cells) and active epithelial albumin transport. In addition we have examined the effects of endothelin on submucosal gland secretion and albumin transport pre-stimulated with the muscarinic agonist methacholine and the alpha-adrenoceptor agonist phenylephrine. The effects of the Ca2+ channel blocker nifedipine on the responses to endothelin have also been assessed. 3. Endothelin (0.1-100 nM) produced concentration-dependent increases in intraluminal tracheal pressure indicating smooth muscle contraction, and in the negativity of the transepithelial p.d. These effects were partially inhibited by nifedipine (10 microM). 4. Endothelin (0.01-100 nM) had no significant effect on baseline rates of mucus, lysozyme or albumin outputs, but produced concentration-dependent reductions in maintained methacholine- and phenylephrine-induced mucus, lysozyme and albumin outputs. In general endothelin was more potent against methacholine-induced effects. All of the concentration-response curves for endothelin were shallow and some appeared to be biphasic, suggesting the possibility of more than one mechanism of action of endothelin. 5. The effects of endothelin (at concentrations greater than 1 nM) on phenylephrine-induced mucus volume, lysozyme and albumin outputs were significantly inhibited by nifedipine. Similarly the effect of endothelin (greater than 1 nM) on methacholine-induced mucus volume and albumin outputs (but not lysozyme output) was attenuated by nifedipine. Similarly the effect of endothelin (>1 nM) on methacholine-induced mucus volume and albumin outputs (but not lysozyme output) was attenuated by nifedipine. The effects of endothelin (at concentrations <1 nM) on methacholine and phenylephrine-induced responses were generally not affected by nifedipine.6. Thus, endothelin contracts ferret tracheal smooth muscle and increases transepithelial p.d. at least in part by opening dihydropyridine-sensitive Ca2+ channels. Endothelin does not directly stimulate submucosal gland secretion or epithelial albumin transport, but inhibits methacholine- and phenylephrineinduced secretion and transport. The inhibitory effects produced by higher concentrations of endothelin may be mediated partially by activation of dihydropyridine-sensitive Ca2+ channels, although the explanation for this is not clear. The mechanism of action of endothelin in attenuating stimulated secretion and epithelial transport at lower concentrations is unknown.
Albumins↗
Laser-Doppler measurement of tracheal mucosal blood flow: comparison with tracheal arterial flow.
Blood flow in the tracheal mucosa (Qm) has been measured by laser-Doppler flowmetry in anesthetized sheep and dogs. The values have been compared with tracheal arterial inflow (Qtr) by use of an electromagnetic flow probe and with tracheal arterial perfusion pressure (Ptr) produced by mechanical perfusion. Changes in blood flow were caused by injections of methacholine, phenylephrine, and histamine into the perfusion circuit. These interventions produced a range of measurements for each animal. Correlations of Qm against Qtr were significant in two of five animals (R = 0.03-0.93); correlations of Qm against Ptr were significant in two of four animals (R = 0.56-0.96). Percent changes in Qtr were generally much larger than those of Qm, and there was considerable variability between Qm and either Qtr or Ptr. Qm reflected the same vascular changes as Ptr or Qtr in 28 interventions and showed an opposing change in 4 cases. In 11 interventions, changes measured by Ptr or Qtr were not reflected by any changes in Qm. Thus qualitative changes in tracheal perfusion measured with these methods were usually the same; quantitatively the three methods showed great differences. These differences may reflect different regulatory mechanisms in various components of the tracheal vasculature or different technical aspects of the methods used.
Animals↗
Tracheal vascular and smooth muscle responses to air temperature and humidity in dogs.
Twenty-five dogs were anesthetized, paralyzed, and artificially ventilated. Their cranial tracheal arteries were perfused bilaterally with blood at constant flow, and the perfusion pressures (Patr) were measured. Tracheal smooth muscle function was assessed by recording changes in external diameter (delta Dtr). The perfused segment of the trachea was exposed to air at a constant unidirectional airflow of 25 l/min. Group 1 (n = 6) was exposed to cold dry air, ambient room air, and hot dry and hot humid air, each for 10 min with exposures starting from zero flow. The tracheal vascular responses to all four conditions were small vasodilations (delta Patr from -2 to -6%) followed by recovery or small vasoconstrictions. In group 2 (n = 19), exposures to cold dry and hot humid air were preceded and followed by body-temperature fully humidified air. Cold dry air caused a sustained vasodilation (delta Patr -9.0 +/- 1.1%), and hot humid air usually caused a biphasic response: a vasoconstriction (delta Patr 4.4 +/- 1.0%) followed by a vasodilation (delta Patr -5.7 +/- 1.9%). The warm humid air after cold dry air or hot humid air caused a further vasodilation, which lasted a short time after cold dry air (delta Patr -3.7 +/- 0.4%) but greater than 10 min after hot humid air (delta Patr -13.8 +/- 1.4%). In both groups, all exposures that cooled the trachea (cold dry air, ambient room air, and hot dry air) caused smooth muscle contraction, and hot humid air that warmed the trachea caused relaxation.
Animals↗
Changes in tracheal mucosal thickness and blood flow in sheep.
Airway narrowing may be produced by increasing the blood volume of the airway mucosa. Here changes in tracheal mucosal thickness (MTtr) were measured in 10 anesthetized sheep. Arteries to the cervical trachea were isolated, and blood flow (Qtr) was measured with an electromagnetic flow probe. Simultaneous changes in MTtr were measured with a mechanical probe over a fixed cartilage. Arterial injections of phenylephrine produced dose-related falls in Qtr and MTtr with a maximum peak fall in MTtr of -104 +/- 18 (SE) microns. Methacholine, bradykinin, albuterol, and histamine produced dose-related increases in Qtr. The largest peak increase in MTtr of 308 +/- 121 microns was seen with bradykinin. For methacholine, albuterol, and histamine the largest increases in MTtr were 154 +/- 47, 45 +/- 10, and 153 +/- 31 microns, respectively. The increases in MTtr were not always closely dose related. The peak changes in MTtr occurred substantially later than those in Qtr for all the drugs and up to 120 s later for methacholine and bradykinin. Generally, changes in MTtr and Qtr persisted for less than 10 min; at the higher doses of bradykinin increases in MTtr lasted for up to 15 min. Changes in MTtr were most closely associated in time with changes in Qtr for the vasoconstrictor phenylephrine. These changes in MTtr would alter airway resistance little in the normal trachea and by substantially more in smaller airways such as the bronchi or in the narrowed trachea. Changes in mucosal thickness may be due not only to changes in tracheal blood volume but may also reflect the effects of tissue edema and mucus secretion.
Airway Resistance↗
Ca2+ mobilization with leukotriene A4 and epoxytetraenes in human neutrophils.
The biosynthesis of leukotrienes and lipoxins involves epoxide-containing intermediates which may be subject to several routes of transcellular metabolism. We have examined the capacity of leukotriene A4 (LTA4) and 15S-hydroxy-5,6-oxido-7,9,13-trans-11-cis-eicosatetraenoic acid [5(6)-epoxytetraene] to stimulate the mobilization of free cytosolic calcium [( Ca2+]i) in human blood neutrophils. To gain insight into structure-activity relationships, a putative intermediate in lipoxin biosynthesis, 5S-hydroxy-14,15-oxido-6,10,12-trans-8-cis-eicosatetraenoic acid [14(15)-epoxytetraene], was prepared by total synthesis. When added to fura-2 loaded neutrophils, each of these compounds provoked a rapid and transient increase in [Ca2+]i (maximum by 8 sec) which returned to baseline within 60-90 sec. Ca2+ mobilization with LTA4 was dose dependent and, at 1 microM, the efficacies of LTA4 and LTB4 were quantitatively similar. The 5(6)-epoxytetraene and 14(15)-epoxytetraene were less potent than LTA4. Prior exposure of the cells to ethyleneglycolbis(aminoethylether)tetra-acetate (EGTA) (60 sec, 3 mM) did not diminish either the amplitude or the extent of [Ca2+]i elicited by LTA4. Methyl esters of LTA4 and 5(6)-epoxytetraene were less potent than their corresponding free acids, whereas the free acid of 14(15)-epoxytetraene and its methyl ester were quantitatively similar. Results from alcohol trapping studies showed that these epoxides were intact during the initial phase of Ca2+i mobilization (t0-10 sec) stimulated by LTA4, 5(6)-epoxytetraene, and 14(15)-epoxytetraene. In addition, the individual mixtures of products formed upon aqueous hydrolysis of each of the epoxides did not stimulate changes in [Ca2+]i. In each case, the products formed were identified by physical methods including reverse phase high pressure liquid chromatography, ultraviolet spectroscopy and gas liquid chromatography-mass spectrometry. These results indicate that, when added to human neutrophils, LTA4, 5(6)-epoxytetraene and 14(15)-epoxytetraene each stimulate a rapid mobilization of [Ca2+]i. Moreover, they suggest that intermediates in the biosynthesis of leukotrienes and lipoxins possess intrinsic activities that may serve to amplify cellular responses within their cell of origin or act on adjacent cells during their transcellular metabolism.
Benzofurans↗
Receptors mediating the effects of 5-hydroxytryptamine on the tracheal vasculature and smooth muscle of sheep.
1. The effects of 5-hydroxytryptamine (5-HT) and the selective 5-HT3 receptor agonist 2-methyl-5-HT were examined on the tracheal vasculature in anaesthetised, paralysed and artificially ventilated sheep. The cranial tracheal arteries were perfused with blood at constant flow and perfusion pressure was measured. 5-HT and 2-methyl-5-HT were injected into the arterial perfusate. Changes in tracheal smooth muscle tone were also measured. 2. 5-HT contracted the tracheal smooth muscle. This contraction was not affected by the 5-HT2 receptor antagonist ketanserin, but was blocked by the combined '5-HT1-like' and 5-HT2 receptor antagonist methysergide. 2-methyl-5-HT had no effect on the tracheal smooth muscle. 3. 5-HT had a complex action on the tracheal vasculature producing either a biphasic change (vasoconstriction followed by dilatation) or just a constriction. 2-methyl-5-HT had a weak vasoconstrictor effect. 4. The vasoconstrictions produced by 5-HT and 2-methyl-5-HT were blocked by ketanserin. The vasodilatation produced by 5-HT was resistant to ketanserin but was antagonised by methysergide. 5. Thus 5-HT contracts the tracheal smooth muscle of sheep by stimulating '5-HT1-like' receptors. 5-HT constricts the tracheal vascular bed by stimulating 5-HT2 receptors or dilates the vascular bed by stimulating '5-HT1-like' receptors. 5-HT3 receptors appear not to be involved in the responses of the tracheal vasculature or smooth muscle to 5-HT.
Animals↗
Prostaglandins alter methacholine-induced secretion in ferret in vitro trachea.
The ferret trachea was mounted in an organ bath containing Krebs-Henseleit solution with additional bovine serum albumin (BSA). Tracheal secretions were collected and analyzed for albumin, and lysozyme, a specific marker of serous cell secretion. The total secretion volume and output and concentrations of albumin and lysozyme were calculated. Secretion was stimulated with methacholine (20 microM) (Mch), and the effects of the prostaglandins PGD2, PGE1, and PGF2 alpha on methacholine-induced secretion were studied. All responses were dose dependent. PGF2 alpha at 10(-5) M increased the volume of Mch-stimulated secretion twofold, the lysozyme output sixfold, and concentration over threefold, while decreasing the albumin transport by one-half. PGD2 at 10(-5) M reduced Mch-induced secretion volume to 75% control, increased albumin transport to 135%, without affecting lysozyme secretion. PGE1 at 10(-5) M increased Mch-stimulated albumin transport and concentration over twofold, decreased lysozyme release to less than one-third of control, and had no effect on secretion volume. PGE1 caused the albumin concentration to exceed that of the outer bath, indicating active transport. We conclude that prostaglandins selectively alter tracheal secretion induced by cholinergic stimuli.
Alprostadil↗
Transport of albumin by the rabbit trachea in vitro.
The rabbit whole trachea was mounted in vitro in an organ bath containing Krebs-Henseleit (KH) solution. When the trachea was air filled there was no resting secretion and none was induced by methacholine (0.02 mM). Histology showed that the trachea has very few submucosal glands. When the trachea was filled with KH, with fluorescent bovine serum albumin in the surrounding KH solution, the rate of transport of albumin into the lumen was measured. Methacholine (0.02 mM) and phenylephrine (0.1 mM) more than doubled the output of albumin, and albuterol (0.1 mM) increased it more than fourfold. Cooling the preparation to 4 degrees C decreased the spontaneous output of albumin to less than one-half control and abolished the increase in output due to albuterol. Addition of sodium cyanide (1 mM) to the preparation abolished the increase in albumin transport due to albuterol. Serosal-to-mucosal transport of fluorescent dextran (mol wt 70,000) was less than one-third that of albumin and was not enhanced by methacholine, phenylephrine, or albuterol. Lysozyme output, an index of serous cell secretion, was barely detectable in controls and was not enhanced by any of the drugs. We conclude that the rabbit trachea has no measurable submucosal gland secretion and that it can actively transport albumin into the lumen via the epithelium. The transport rate is enhanced by methacholine, phenylephrine, and especially by albuterol.
Albuterol↗
Effects of neurotransmitters on tracheobronchial blood flow.
Blood flow in the tracheobronchial airways is regulated by three main nervous pathways: 1) sympathetic motor nerves (adrenergic and nonadrenergic); 2) parasympathetic motor nerves (cholinergic and noncholinergic); and 3) afferent or sensory nerves (peptidergic). Noradrenaline is the main adrenergic mediator which produces short-lasting constrictions in both tracheal and bronchial vascular beds and in both arteries and veins. These responses are mediated via alpha-adrenoceptors. The nonadrenergic mediator neuropeptide Y is a vasoconstrictor which produces long-lasting responses with larger doses. Acetylcholine is the principal mediator of the cholinergic nerves and causes short-lasting dilations at all levels of the tracheobronchial circulation (arteries, veins and bronchopulmonary anastomoses). These responses are mediated via muscarinic receptors. Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (in man peptide histidine methionine) are the main mediators of the noncholinergic nerves. Both of them produce vasodilation in the tracheobronchial circulation; VIP can cause longer-lasting responses with larger doses. The afferent or sensory nerves contain tachykinins, i.e. substance P and neurokinins A and B, which are potent vasodilators in the tracheobronchial circulation and also potent inducers of postcapillary permeability. Calcitonin gene-related peptide is another sensory neuropeptide with ability to produce long-lasting vasodilations without affecting microvascular permeability.
Animals↗
Effects of non-neural mediators and allergen on tracheobronchial blood flow.
There are a large number of non-neural mediators released from a variety of cells in the airways. The release of many of these mediators is often enhanced during the inflammatory phase of airway diseases such as asthma. Therefore, they are likely to be important regulators of not only airway smooth muscle tone but also airway blood flow and microvascular permeability. Non-neural mediators have potent and in some cases (histamine, 5-hydroxytryptamine (5HT) complex actions on tracheobronchial blood flow. The blood flow effects of some of these mediators (histamine, 5HT, bradykinin) occur by activation of specific receptors, but may also involve secondary mediators (bradykinin). There are clear species differences in the responses of the tracheobronchial circulation to non-neural mediators. Allergen challenge of the airways changes not only airway smooth muscle tone but also tracheobronchial blood flow. These changes in blood flow (dilation or constriction) seem to be mediated, at least in the sheep, by antigen-induced release of a mixture of prostaglandins and leukotrienes. The type of vascular response observed with antigen challenge partly depends on the balance of mediators released, which again may depend on several factors including the species and the age of the animal.
Allergens↗
Identification of a novel 7-cis-11-trans-lipoxin A4 generated by human neutrophils: total synthesis, spasmogenic activities and comparison with other geometric isomers of lipoxins A4 and B4.
Addition of (15S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE) and the ionophore A23187 (2.5 microM) to human neutrophils led to the formation of both lipoxin A4 and lipoxin B4 as well as a novel 5,6,15-trihydroxyeicosatetraenoic acid. The new compound was identified using an improved isolation and detection system and its basic structure was determined by physical methods. On the basis of biosynthetic considerations, geometric isomers of lipoxin A4 and lipoxin B4 were prepared by total synthesis. Comparison of these synthetic materials with the neutrophil-derived product showed that the new compound is (5S,6R,15S)-trihydroxy-9,11,13-trans-7-cis-eicosatetraenoic acid or the 7-cis-11-trans-isomer of LXA4 (7-cis-11-trans-LXA4). LXA4, 11-trans-LXA4, 7-cis-LXA4 and 7-cis-11-trans-LXA4 all evoked dose-dependent (0.1-10 microM) contractions of the guinea pig lung strip, whereas 6-cis-LXB4 and 6-cis-8-trans-LXB4 relaxed this preparation. LXA4 and 7-cis-LXA4 were approx. 10-times more potent than the compounds with 11-trans geometry. However, all four double-bond isomers of LXA4 caused contractions which, based upon pharmacological evidence, appeared to involve specific activation of the same site as cysteinyl-containing leukotrienes. In conclusion, 7-cis-11-trans-LXA4 was isolated and identified as a novel biologically active eicosanoid formed by human neutrophils.
Airway Resistance↗
Pharmacodynamics of lipoxin A4 in airway smooth muscle.
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Animals↗
Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor.
1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors.
Animals↗