PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Methacholine Chloride”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1986

Relaxation decreases large-airway but not small-airway asthma.

Eleven asthmatic subjects were each offered sixteen sessions of relaxation therapy, consisting of progressive relaxation, desensitization, and EMG biofeedback to the trapezius and frontalis areas, while 9 subjects were offered a complex placebo. Subjects in the relaxation condition showed greater improvement than subjects in the placebo condition in performance on a methacholine challenge test which, as a measure of airway reactivity, reflects degree of asthma. Subjects in both conditions showed improvements in various self-report measures of asthma symptoms and psychopathology. Subject in the relaxation condition reported a significantly greater decrease in frequency of emotional precursors to asthma attacks than subjects in the control condition. Overall improvement on the methacholine challenge test was predicted almost perfectly by heliox spirometry. Only subjects showing predominant large-airway obstruction obstruction improved on the methacholine challenge test. The relative contribution of large airway obstruction to asthma was found to correlate with psychopathology.

Adult↗
PubMed1987

Serotonin release is mediated by muscarinic receptors on duodenal mucosal cells.

Serotonin (5-HT), found in abundance in intestinal enterochromaffin cells, has been shown to be released in response to neural, humoral, and intraluminal stimuli but the mechanisms controlling release are poorly understood. The purpose of this study was to determine whether 5-HT release induced by the muscarinic agonist, methacholine, is mediated by enteric nerves or is a direct action at the mucosal cell level. We mounted rabbit mucosal sheets containing intact submucosal neural elements, but stripped of muscularis propria and myenteric plexus, in modified Ussing chambers and measured the release of 5-HT in response to 5 X 10(-5) M methacholine added to both mucosal and serosal surface bathing solutions, in the presence and absence of selective neural blockade with 1 X 10(-6) M tetrodotoxin. 5-HT release in control tissues (no drugs) as measured by radioimmunoassay was 25.7 +/- 6 ng/cm2/30 min (mean +/- SEM). In the presence of mucosal and serosal methacholine, total 5-HT release increased significantly (P less than 0.05) to 66.7 +/- 9 ng/cm2/30 min. When tetrodotoxin alone was applied, 5-HT release significantly increased to 55.2 +/- 9 ng/cm2/30 min compared to matched control. In the presence of tetrodotoxin, methacholine increased 5-HT release to 79.3 +/- 9 ng/cm2/30 min, which was significantly greater than with tetrodotoxin alone. These results provide evidence of an inhibitory neural regulation of basal 5-HT release since release increased in the presence of neural blockade. They also suggest that a muscarinic receptor at or near the enterochromaffin cells mediates mucosal 5-HT release since 5-HT is further increased by methacholine even in the presence of neural blockade.

Animals↗
PubMed1982

Comparison of muscarinic and beta adrenergic receptors between bovine peripheral lung and tracheal smooth muscles: a striking difference in the receptor concentration.

This study was undertaken to compare the activity of muscarinic and beta adrenergic receptors in bovine peripheral lung to the corresponding receptor activity in tracheal smooth muscle. We used [3H] quinuclidinyl benzilate (QNB) and [3H]dihydroalprenolol (DHA) to measure muscarinic and beta receptor activity, respectively. Binding to QNB and DHA at 25 degrees C was rapid, reversible, saturable and of high affinity. The order of potency for cholinergic and adrenergic agents competing for binding was compatible with muscarinic and beta 2 adrenergic potencies. We found that the concentration of muscarinic receptor binding sites was 37-fold greater in the tracheal muscle preparation (2805 +/- 309 fmol/mg protein) than in the peripheral lung preparation (76 +/- 28 fmol/mg protein). Unlike muscarinic receptors, the lung contained 8-fold higher concentration of the beta adrenergic receptors than did the tracheal muscle (1588 +/- 417 vs. 199 +/- 42 fmol/mg protein). The dissociation constant or the agonist's inhibitory constant (Ki) for either receptor binding site, however, was not significantly different between the two tissues. Furthermore, in vitro contraction studies showed that the response of tracheal muscle strips to methacholine was markedly greater than the response of peripheral lung strips, a finding consistent with the QNB binding result. The muscle but not the peripheral lung strip exhibited a relaxing response to epinephrine. Our data indicate a striking quantitative difference in muscarinic and beta adrenergic receptors between lung tissue and tracheal muscle, and that each receptor in the lung is qualitatively similar to the corresponding receptor in the muscle.

Animals↗
PubMed1984

Metabolism of inositol phosphates in parotid cells: implications for the pathway of the phosphoinositide effect and for the possible messenger role of inositol trisphosphate.

Rat parotid acinar cells were used to investigate the time course of formation and breakdown of inositol phosphates in response to receptor-active agents. In cells preincubated with [3H]inositol and in the presence of 10 mM LiCl (which blocks hydrolysis of inositol phosphate), methacholine (10(-4)M) caused a substantial increase in cellular content of [3H]inositol phosphate, [3H]inositol bisphosphate and [3H]inositol trisphosphate. Subsequent addition of atropine (10(-4) M) caused breakdown of [3H]inositol trisphosphate and [3H]inositol bisphosphate and little change in accumulated [3H]inositol phosphate. The data could be fit to a model whereby inositol trisphosphate and inositol bisphosphate are formed from phosphodiesteratic breakdown of phosphatidylinositol bisphosphate and phosphatidylinositol phosphate respectively, and inositol phosphate is formed from hydrolysis of inositol bisphosphate rather than from phosphatidyl-inositol. Consistent with this model was the finding that [3H]inositol trisphosphate and [3H]inositol bisphosphate levels were substantially increased in 5 sec while an increase in [3H]inositol phosphate was barely detectable at 60 sec. These results indicate that in the parotid gland the phosphoinositide cycle is activated primarily by phosphodiesteratic breakdown of the polyphosphoinositides rather than phosphatidyl-inositol. Also, the results show that formation of inositol trisphosphate is probably sufficiently rapid for it to act as a second messenger signalling internal Ca2+ release in this tissue.

Animals↗
PubMed1984

A comparison of the antimuscarinic effects of pirenzepine and N-methylatropine on ganglionic and vascular muscarinic receptors in the rat.

The antimuscarinic properties of pirenzepine and N-methylatropine were evaluated in two intact preparations by measuring A) the inhibition of increase in mean arterial pressure evoked by McN-A-343 in pithed rats through activation of ganglionic muscarinic receptors and B) the inhibition of fall in arterial pressure evoked by methacholine in anaesthetized rats through activation of vascular muscarinic receptors. To characterize the antimuscarinic potencies of pirenzepine and N-methylatropine, for both antagonists doses were calculated that produce a 10-fold shift to the right of the dose-response curves for A) the pressor response to McN-A-343 (i.v. administration) in pithed rats (D10-p.r.) and B) for the depressor effect to methacholine (i.v. administration) in anaesthetized rats (D10-an.r.), respectively. Whereas N-methylatropine was virtually equieffective in blocking both muscarinic responses (D10-an.r./D10-p.r. approximately equal to 1), pirenzepine, however, was considerably more potent at ganglionic than at vascular muscarinic receptors (D10-an.r./D10-p.r. approximately equal to 16). These data confirm the existence of excitatory ganglionic muscarinic receptors with high affinity for pirenzepine (M1) and provide evidence for the presence of M2 receptors - receptors which show a low sensitivity to pirenzepine - on vascular smooth muscle cells. To further characterize the anticholinergic properties of pirenzepine, its effect on the pressor response to DMPP, a nicotinic ganglionic stimulant, was investigated in pithed rats. A high dose of pirenzepine (1.13 mumol/kg), given i.v., did not affect nicotinic ganglionic transmission.

Animals↗
PubMed1986

The dependence of airway smooth muscle on extracellular Ca2+ for contraction is influenced by the presence of cartilage.

Isolated guinea-pig and rabbit airway smooth muscle preparations lacking cartilage are less able to contract, in response to methacholine, histamine and K+, in the absence of extracellular Ca2+ than cartilage-containing preparations removed from the same animal. Cartilage apparently provides utilizable Ca2+ for contraction of airway smooth muscle. The presence of cartilage, therefore, affects the apparent dependence of the isolated smooth muscle on extracellular Ca2+ for contraction.

Animals↗
PubMed1986

The effect of verapamil is reduced in isolated airway smooth muscle preparations lacking the epithelium.

The effect of epithelium removal on the reactivity of rabbit airway smooth muscle to bronchoactive agents and on the effect of verapamil was studied in vitro using preparations from several levels within the respiratory tree, i.e., trachea, primary (10) and secondary (20) bronchus. Methacholine contracted tissues from all three levels of airway. Histamine contracted strips from 20 bronchus, had an inconsistent action in strips from 10 bronchus and was without effect in tracheal preparations. K+ contracted tissues from the trachea and 10 bronchus, and had a mixed action in 20 bronchial strips. Removal of the epithelial cell layer variably affected the reactivity of the smooth muscle to the three agents studied. In 20 bronchus, epithelium removal potentiated responses to histamine and methacholine. In 10 bronchus, only responses to methacholine were consistently augmented. In tracheal preparations epithelium removal did not alter the reactivity of the tissue to any agent examined. Verapamil (1 microM) attenuated responses to all agents and increased in its potency from tracheal through 10 to 20 bronchial preparations. Following epithelium removal, verapamil was substantially less effective in 20 bronchi, yet its effects were unchanged in the trachea. The results indicate that the epithelial cell layer modulates airway smooth muscle reactivity; this phenomenon is apparently widespread in mammals, the modulatory effect is more prominent in the smaller airways, and the magnitude of the effect of verapamil on airway smooth muscle is, in part, related to the presence of the epithelium.

Animals↗
PubMed1987

Nicotinic receptor stimulation enhances enkephalin-like peptides processing in chromaffin cells.

Acute stimulation of chromaffin cells in cultures with acetylcholine (ACh), 1,1-dimethyl-4-phenylpiperazinium (DMPP), or high potassium gave rise to a significant increase in the release of [Met5]-enkephalin immunoreactive material (ME-IRM) into the assay medium. The cellular content of ME-IRM following the actual release induced by these secretagogues remained constant suggesting the replenishment of the cellular peptides. The repletion of the peptides may occur through an enhancement of the processing rate of the proenkephalin precursor. Furthermore, the increase in secretion as well as the repletion of the cellular ME-IRM were calcium-dependent and were inhibited by the nicotinic receptor antagonist, hexamethonium, but not by atropine. These results indicate that secretion and repletion of the peptides are tightly coupled and activated by nicotinic receptor stimulation.

Acetylcholine↗
PubMed1988

A novel muscarinic receptor antagonist AF-DX 116 differentially blocks slow inhibitory and slow excitatory postsynaptic potentials in the rabbit sympathetic ganglia.

Muscarinic, slow postsynaptic potentials (s-epsp and s-ipsp) in the rabbit superior cervical ganglia were shown to be differentially depressed by a novel cardioselective M2-type antagonist AF-DX 116: it antagonized the s-ipsp with IC50 value of 1.5 X 10(-7) M, which is 16-fold more potent in depressing the s-ipsp than the s-epsp. A hyperpolarizing component in the biphasic potential changes induced by a muscarinic agonist, methacholine, was selectively eliminated by this antagonist. AF-DX 116 was thus shown to be an useful tool for discriminating the M2-type muscarinic responses from those of M1-type in the nervous system.

Action Potentials↗
PubMed1984

Effects of bronchoconstriction on breathing during normoxia and hypoxia in anesthetized cats.

The effect of an increase in bronchomotor tone on control of breathing during both normoxia and hypoxia, and the role of vagal afferents in regulating these responses were studied in 15 anesthetized cats. Minute ventilation (VE) was measured with a pneumotachograph connected in series with a tracheal cannula. Total diaphragmatic EMG activity per minute (means p X f, peak EMG moving average X respiratory frequency) was measured to assess the central inspiratory drive. Bronchoconstriction was generated by inhalation of methacholine aerosol (10-30 breaths, 0.5% solution) which increased total lung resistance to approximately 400% of the control value. Transient hypoxia was induced by allowing the cats to rebreathe a hypoxic gas mixture (4.5% O2 balanced N2) for approximately 1 min. During normoxia, bronchoconstriction increased VE from a baseline of 100 to 129 +/- 7% (mean +/- SEM; P less than 0.05) and increased (means p X f) from 100 to 174 +/- 16% (P less than 0.01). During hypoxia, the response of (means p X f) to bronchoconstriction (404 +/- 40%) was still greater than without bronchoconstriction (306 +/- 35%; P less than 0.01), but the responses of VE were not significantly different between these two conditions (P greater than 0.05). After sectioning both vagus nerves the bronchoconstriction-induced increase in central inspiratory drive was either reduced (during normoxia) or abolished (during hypoxia). These results suggest that stimulation of vagal bronchopulmonary afferents are involved in regulating the ventilatory responses to bronchoconstriction. Other non-vagal factors, such as intrinsic properties and reflex responses of the respiratory muscles, may also contribute, in part, to the observed responses.

Anesthesia↗
PubMed1984

The relationship between bronchial hyperresponsiveness to methacholine and airway smooth muscle structure and reactivity.

The airway responsiveness of a group of 25 patients scheduled for lung resection was studied. 10 of 25 patients had a greater than or equal to 20% fall in FEV1 in response to inhaled methacholine (responders), with PD20 FEV1 values ranging from 0.6 to 7.3 mumol. Methacholine did not induce a 20% fall in FEV1 in 15 patients (non-responders). The sensitivity to carbachol and histamine of the bronchial smooth muscle resected from these patients was similar in tissue from responders and non-responders. There was no correlation between in vivo responsiveness to methacholine and in vitro sensitivity to carbachol or histamine. The volume of smooth muscle in some of these airway preparations was quantitated. There was a significant correlation between the maximum tension change in response to histamine and the volume of smooth muscle in each airway. There was no similar correlation for carbachol. The in vivo responsiveness to methacholine and in vitro sensitivity to histamine or carbachol was not related to the degree of inflammation in the airways studied. It is concluded that in vivo responsiveness cannot be explained in terms of smooth muscle sensitivity and that there may be differences between histamine and carbachol in the mechanism of contraction of airway smooth muscle.

Adult↗
PubMed1985

Alteration of airway reactivity by mucus.

In 11 beagles with permanent tracheostomies we investigated whether mucus hypersecretion alters airway reactivity to inhaled aerosols. Mucus was collected from the dogs while awake by resting a cytology brush on the lower tracheal mucosa; the mucus collection rate was used as an index of mucus flux. Mucus linear velocity was determined under light sedation by bronchoscopically observing the rate of particle clearance in the trachea. Mucus depth was then computed from the flux and velocity. On a separate occasion, under pentobarbital anesthesia, methacholine aerosols (1 min duration) were given at 10 min intervals in doubling doses up to at least 2 mg/ml. Pulmonary resistance RL was determined prior to and 2 min after each dose. After a 1 h pause, methacholine was infused at a constant rate of 40 micrograms X kg-1 X min-1 for 10 min. This dose produced a plateau in RL after approximately 3 min; the mean rise in RL was similar to that achieved with the 2 mg/ml aerosol. The infusion response Rinf was defined as the change in RL 4-5 min post infusion; the aerosol response Raer was defined as the change in RL 2 min post 2 mg/ml aerosol. There was no significant correlation between Rinf and Raer, nor between either Rinf or Raer and mucus flux. There was, however, a strong positive association between Rinf/Raer and mucus flux and a similar positive association between Rinf/Raer and mucus depth. These associations indicate that dogs with elevated secretion levels are relatively unresponsive to aerosolized as opposed to infused methacholine. Thus, to the extent that infusion reactivity reflects innate airway reactivity, the reactivity to inhaled aerosol may underestimate the true value when mucus hypersecretion occurs.

Aerosols↗
PubMed1986

Airway responses to methacholine and histamine in basenji greyhounds and other purebred dogs.

To investigate whether airway hyperresponsiveness is a general characteristic of either the basenji or the greyhound ancestry of the basenji-greyhound (BG) dog and to determine whether airway hyperresponsiveness of the BG dogs in specific for methacholine, we compared pulmonary responsiveness to increasing doses of aerosols of histamine and methacholine in 17 BG dogs, 5 unrelated purebred basenjis and 5 unrelated greyhounds. BG dogs were hyperresponsive to both methacholine and histamine compared to basenjis and greyhounds. There was a significant correlation between histamine compared to basenjis and greyhounds. There was a significant correlation between histamine and methacholine responsiveness (r = 0.70, P less than 0.0001) in the dog population. We conclude that airway hyperresponsiveness characteristic of the BG dog is not a general characteristic of the basenji or greyhound breed and occurs to histamine as well as to methacholine.

Aerosols↗
PubMed1986

Mechanisms of gas loss from normal and hyperinflated excised guinea pig lungs.

Increased pulmonary gas trapping was produced by in vivo inhalation exposures of guinea pigs to bronchoconstrictive aerosols. Both normal (filtered air-exposed) and hyperinflated excised lungs lost about 20% of their initial volume by 4 h; gas loss was more rapid during the first 60 min (early period) than the following 180 min (late period). During both periods, absolute rates of gas loss were positively correlated (P less than 0.001) with initial excised lung gas volumes (ELGVs). Tracheal foam movement was observed in most of the hyperinflated lungs, but only during the early period. Occlusion of the trachea reduced gas loss during the early period, but not the late. Gas volumes increased in lungs of animals exposed to SF6:O2 (tracheas tied), and decreased most rapidly in lungs of animals exposed to He:O2 (tracheas tied). Our results suggest that a major part of the early gas loss from excised guinea pig lungs occurs via the trachea and may be influenced by airway foam or menisci formation. After 60 min, airways may be closed and gas loss may occur via transpleural diffusion.

Airway Resistance↗