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At least 811 records · Page 45Linked to original sources
PubMed1979

Depressed cyclic AMP levels in airways smooth muscle from asthmatic dogs.

We tested mongrel dogs by intradermal injection and tracheobronchial aerosol challenge with Ascaris suum antigen extract. All dogs were skin-test positive but could be segregated, on the basis of airways resistance measurements, into "asthmatic" (bronchoreactive) and "nonasthmatic" (nonbronchoreactive) groups. By using tracheal rings from these dogs, we measured the abilities of the beta-adrenergic agonist, isoproterenol, to relax tracheal smooth muscle contracted by methacholine and to cause cyclic AMP (cAMP) accumulation in the presence and absence of methacholine. The magnitude of relaxation induced by any concentration of isoproterenol was always less in the smooth muscle from "asthmatic" dogs. In the same tissues the concentrations of cAMP after in vitro equilibration, but prior to isoproterenol addition, were significantly less in the "asthmatic" than "nonasthmatic" samples. The accumulation of cAMP due to isoproterenol was similar in both groups for every dose of isoproterenol so that the initial difference between groups in cAMP concentration was maintained in an additive fashion over the entire dose-response curve. Total protein content of trachealis muscles from both groups of dogs was the same. We conclude that beta-adrenergically sensitive adenylate cyclase is not impaired in tracheal smooth muscle from "asthmatic" dogs; rather, the basal concentration of cAMP is depressed in "asthmatic" airway smooth muscle, and this difference is maintained throughout the isoproterenol dose-response curve. The depressed intracellular cAMP concentrations may be related to the decreased relaxation induced by isoproterenol in the "asthmatic" tracheal smooth muscle.

Animals↗
PubMed1983

Pancreatic epithelium is permeable to sucrose and inulin across secretory cells.

The pancreatic epithelium is permeable to both sucrose and inulin and becomes more permeable when protein secretion by the gland is stimulated. Because these molecules are not thought to enter cells, it has been assumed that their movement across the epithelium from interstitial to ductal fluid, as well as the increase in that flux that is observed during augmented protein secretion, is due to their passage through paracellular shunts. In the present experiments we have considered the alternative possibility that sucrose and inulin travel through the cells of the secretory epithelium instead of, or in addition to, their passage through paracellular shunts. The data support this view and suggest that the pancreas is unusually permeable to water soluble molecules of substantial size by means of a transcellular pathway.

Animals↗
PubMed1989

Convergence and divergence of neurotransmitter action in human cerebral cortex.

The postsynaptic actions of acetylcholine, adenosine, gamma-aminobutyric acid, histamine, norepinephrine, and serotonin were analyzed in human cortical pyramidal cells maintained in vitro. The actions of these six putative neurotransmitters converged onto three distinct potassium currents. Application of acetylcholine, histamine, norepinephrine, or serotonin all increased spiking by reducing spike-frequency adaptation, in part by reducing the current that underlies the slow after hyperpolarization. In addition, application of muscarinic receptor agonists to all neurons or of serotonin to middle-layer cells substantially reduced or blocked the M-current (a K+ current that is voltage and time dependent). Inhibition of neuronal firing was elicited by adenosine, baclofen (a gamma-aminobutyric acid type B receptor agonist), or serotonin and appeared to be due to an increase in the same potassium current by all three agents. These data reveal that individual neuronal currents in the human cerebral cortex are under the control of several putative neurotransmitters and that each neurotransmitter may exhibit more than one postsynaptic action. The specific anatomical connections of these various neurotransmitter systems, as well as their heterogeneous distribution of postsynaptic receptors and responses, allows each to make a specific contribution to the modulation of cortical activity.

Adenosine↗
PubMedDate not supplied

Airway responses to 2.0 ppm nitrogen dioxide in normal subjects.

Nitrogen dioxide (NO2) is a common indoor air pollutant. To characterize the acute respiratory responses to this gas, 18 nonsmoking normal subjects (mean age +/- standard deviation [SD] = 25 +/- 4 yr) were exposed to filtered air or 2 ppm NO2 gas for 1 hr in a 30-m3 environmental chamber on different days, typically 1 wk apart, in a double-blind randomized fashion. Lung function tests included forced vital capacity, forced expiratory volume in one second, partial expiratory flow at 40% of vital capacity (Vp40), functional residual capacity, and specific airway conductance, and were measured before and after exposure. Airway reactivity to methacholine inhalation was determined within 45 min of each exposure. The dose of methacholine in mg/ml to cause a 40% decrease in specific airway conductance (PD40) was measured. Airway reactivity to methacholine aerosol increased significantly after NO2, which is shown by a decrease in the concentration of methacholine; PD40 (AIR) = 101 +/- 44, PD40 (NO2) = 81 +/- 45 mg/ml, p = .003. No significant changes were noted in the lung function tests after NO2 exposure. These findings indicate that normal nonsmokers exposed to 2.0 ppm NO2 for 1 hr develop an increase in airway reactivity to methacholine aerosol, which is not associated with changes in lung volumes, flow rates, or respiratory symptoms.

Adolescent↗
PubMedDate not supplied

Acute airway narrowing in monkeys from challenge with 2.5 ppm formaldehyde generated from formalin.

Nine adult male Cynomolgus monkeys (Macaca fascicularis) were exposed for 10 min to 2.55 +/- 0.03 ppm formaldehyde (HCHO; mean +/- standard error of the mean, SEM) generated from formalin with a newly developed HCHO challenge system. The generation system was capable of producing highly stable HCHO vapor concentrations with fluctuations of HCHO concentrations of less than +/- 5%. The experimental design included pre-exposure methacholine challenge to determine if responses to HCHO were associated with pre-existing bronchial hyperreactivity. Significant changes in average pulmonary flow resistance (RL) were observed (compared to control RL values) at 2 (p less than 0.01), 5 (p less than 0.01), and 10 min (p less than 0.005) post-HCHO challenge. Pre-challenge RL values (mean +/- SEM) were 11.3 +/- 1.4 cm H2O.l/s, while at 2, 5, and 10 min after HCHO challenge, values were 16.1 +/- 2.1, 16.9 +/- 2.8 and 20.0 +/- 3.4 cm H2O.l/s, respectively. Methacholine challenge data suggest that reactions to HCHO tend to be greater in monkeys hyperreactive to methacholine, but the relationship does not reach statistical significance in this small series of animals. These data indicate that significant pulmonary function deficits occur immediately after challenge with 2.55 ppm HCHO vapor in monkeys.

Administration, Inhalation↗
PubMed1990

Epidermal growth factor and haptocorrin in nasal secretion.

We report that nasal secretion contains the growth-promoting peptide epidermal growth factor (EGF) and a cobalamin-binding protein. Based on its amino-terminal sequence the cobalamin binding protein is classified as haptocorrin (HC). We have investigated the concentration of these components, the volume secreted, and the concentration of total protein after nasal challenge with methacholine, methacholine + ephedrine, histamine and serotonin. The EGF and HC concentrations do not differ for the four challenge agents employed. Range and median for all values obtained are 0.1-2.5 (0.7) nmol/l (n = 49) for EGF and 50-405 (190) nmol/l (n = 63) for HC. After challenge with methacholine the amount of secretion (80-630 (200) mg (n = 14) and the protein concentration (1.5-7.8 (3.5) g/l (n = 14] are lower than for any other challenge. After challenge with serotonin or histamine the amount secreted is 60-1125 (480) mg (n = 39). The concentration of protein is significantly higher (p less than 0.01) after challenge with serotonin (1.4-56.0 (17.0) g/l (n = 18] than after challenge with histamine (2.0-25.0 (5.0) g/l (n = 20].

Adult↗
PubMed1978

Effects of atropine and methacholine on deposition and clearance of inhaled particles in the donkey.

The influence of sympathetic and parasympathetic controls on regional particle deposition and mucociliary clearance rates was studied in the donkey in vivo. The deposition and clearance characteristics for gamma-tagged monodisperse ferric oxide microspheres were determined for inhalation tests after atropine and methacholine injections and were compared with the characteristics determined for control tests with the same animals and aerosols. Additional tests were performed in which methacholine was injected immediately after the test aerosol inhalation and 2 1/2 h before the particle inhalation. Particle deposition is shifted distally by atropine. Methacholine produces a proximal shift initially and a distal shift 2 1/2 h later. Atropine slows mucociliary transport. Methacholine produces an acceleration in bronchial clearance initially but causes a reduced rate of clearance 2 1/2 h later. Atropine slows mucociliary transport. Methacholine produces an acceleration in bronchial clearance initially but causes a reduced rate of clearance 2 1/2 h later. It also produces an initial surge in tracheal transport, which frequently leads to tracheal mucus refluxing and thereby an increase in average tracheal residence time. The drugs were used to modify the normal deposition and clearance characteristics of a particular animal so that they resembled the normal characteristics of a different animal, suggesting that much of the large intersubject variability may be attributable to different levels of autonomic tone.

Aerosols↗
PubMedDate not supplied

Effects of 0.2 ppm nitrogen dioxide on pulmonary function and response to bronchoprovocation in asthmatics.

To study the respiratory effects of nitrogen dioxide (NO2) at ambient concentrations, we exposed 31 asthmatic volunteers to purified air (control) and to 0.2 ppm NO2 for 2-h periods with light intermittent exercise. Bronchial reactivity (loss of forced expiratory performance in response to graded doses of methacholine chloride aerosol) was determined postexposure, using a newly developed apparatus that allowed accurate quantitation of methacholine dose. Forced expiratory performance, total respiratory resistance, and symptoms were also recorded immediately pre- and postexposure (prior to methacholine challenges). No significant direct effect of NO2 exposure on forced expiratory function or total respiratory resistance was observed. Symptoms showed a small significant (p less than 0.05) excess in purified air relative to NO2 exposures. Individual responses to methacholine varied greatly. About two-thirds of the subjects showed greater response after NO2 than after purified air, but the mean excess response was small. Mean changes attained significance in some but not all applicable statistical tests. Thus we cannot conclude unequivocally that NO2 exposure increased bronchial reactivity in this group, although there was some tendency in that direction.

Adolescent↗
PubMed1986

Interactions of a water extract of cotton bract with dog isolated airway smooth muscle.

The inhalation of cotton dust by cotton-mill workers causes byssinosis, a disease characterized by chest tightness and other symptoms indicative of bronchoconstriction. In the present study the dog isolated trachealis smooth muscle preparation was employed to examine the ability of a crude, water extract of cotton bracts (CBE) to (1) cause contractile responses mediated by receptors, (2) modify responses of the tissue to a number of excitatory and inhibitory agents, and (3) alter responsiveness of the preparations to electrical field stimulation mediated by intrinsic cholinergic, excitatory nerves and adrenergic, inhibitory nerves. CBE evoked contraction of the tissues by an action that did not involve muscarinic, histamine, or 5-hydroxytryptamine receptors. The maximum tissue responses to exogenous histamine, 5-hydroxytryptamine, and isoproterenol were enhanced significantly in the presence of CBE, while those to KCl and methacholine were unaffected. The sensitivities (EC50 values) of the tissues to these agents were not, however, altered by CBE. Contractions induced by cholinergic nerve stimulation were increased in the presence of CBE, via a mechanism that appears, at present, to result from a prejunctional facilitation of acetycholine release. Relaxations to adrenergic nerve stimulation were not affected by CBE. Results suggest that, in addition to its direct, contractile activity, CBE can alter indirectly the responsiveness of the tissue to a number of endogenous mediator substances. Intrinsic, cholinergic excitatory nerves may be a target for the acute action of CBE as well.

Animals↗
PubMed1986

Effects of a cotton bract extract on guinea pig isolated airway smooth muscle.

The effects of a water extract of cotton bracts (CBE) on guinea pig isolated trachealis smooth muscle was studied. The ability of CBE to evoke tension responses, to modify tissue reactivity to excitatory and inhibitory agents, and to modify electric field stimulation-induced neurogenic responses was evaluated. CBE caused contraction in low concentrations, which were not mediated by histamine H1-, muscarinic, or 5-hydroxytryptamine (5-HT) receptors, and caused relaxation in high concentrations. In the presence of CBE, the maximum contractile response to 5-HT and the sensitivity to KCl were reduced. The maximum relaxation responses and sensitivities to adenosine and ATP were increased by CBE. In contrast, contractile responses to histamine and methacholine and relaxation responses to isoproterenol were unaffected. Neurogenic cholinergic excitatory responses and neurogenic adrenergic responses did not appear to be affected by CBE. However, the relaxant effect of nonadrenergic inhibitory nerve stimulation was increased in the presence of CBE. These findings differ from previous ones observed in our laboratory for dog isolated trachealis smooth muscle preparations, which indicates that the effects of CBE in isolated airways is species-dependent. Virtually all of the contractile activity of CBE was dialyzable (molecular weight less than 14,000) and retained in ashed samples. Inorganic constituents may contribute to the spasmogenic activity of CBE.

Adenosine↗
PubMed1987

Airway responses to nitrogen dioxide in asthmatic subjects.

Nitrogen dioxide is a common indoor air pollutant. In order to characterize the respiratory responses to this gas, 10 asthmatics (mean age +/- SD = 30 +/- 8 yrs) were exposed to air and 0.5 ppm NO2 gas for 1 h in a 30-m3 environmental chamber on different days in a double-blind randomized fashion. The forced vital capacity, (VC), functional residual capacity, forced expiratory volume in 1 s, partial expiratory flow at 40% VC (Vp 40), and specific airway conductance were measured before and after exposure. Airway reactivity to methacholine inhalation was determined after each exposure. The dose of methacholine in milligrams per milliliter to cause a 40% decrease in Vp 40 was measured. None of the subjects reported any significant symptoms after exposure. Significant potentiation of airway reactivity was noted after NO2 exposure in asthmatic subjects as a group [PD40(AIR) = 9.2 +/- SD 15.0 versus PD40(NO2) = 4.6 +/- SD 8.2 mg/ml, p = 0.042]. No significant changes were noted in other lung functions after NO2 exposure. These findings indicate that asthmatics exposed to 0.5 ppm NO2 develop heightened airway reactivity.

Adult↗
PubMed1990

Dose-response relationship of ozone-induced airway hyperresponsiveness in unanesthetized guinea pigs.

The effect of ozone dose (the product of ozone concentration and exposure time) on airway responsiveness was examined in unanesthetized, spontaneously breathing guinea pigs. Airway responsiveness was assessed by measuring specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine (Mch) aerosol (the concentration of Mch required in order to double the baseline sRaw: PC200Mch). The airway responsiveness was measured before and at 5 min, 5 h, and 24 h after exposure. A 30-min exposure to 1 ppm ozone (dose 30 ppm.min) did not change PC200Mch at any time after exposure. Both a 90-min exposure to 1 ppm ozone and a 30-min exposure to 3 ppm ozone, which are identical in terms of ozone dose (90 ppm.min), decreased PC200Mch to a similar degree. A 120-min exposure to 3 ppm ozone (360 ppm.min) produced a much greater decrease of PC200Mch at 5 min and 5 h after exposure, compared with low-dose exposure. There was a significant correlation between ozone dose and the change in airway responsiveness. In all groups, the baseline sRaw was increased by approximately 50% at 5 min after exposure, but there was no correlation between the changes in PC200Mch and the baseline sRaw. This study suggests that ozone-induced airway hyperresponsiveness in guinea pigs is closely related to ozone dose.

Aerosols↗