Showing papers by "Peter J. Barnes published in 1982"

Localization of β -adrenoreceptors in mammalian lung by light microscopic autoradiography

Abstract: β-Adrenergic agonists regulate a variety of lung functions including relaxation of airway smooth muscle, secretion of mucus1, release of surfactant2 and modulation of mediator release from mast cells3. Assays of the direct binding of radio-labelled β-adrenergic antagonists to homogenates of whole lung from several species have revealed a very high density of β-adrenoreceptors, but the cellular location of these receptors has not been determined4–7. Using a technique previously used to study distribution of receptors in the brain8,9 we report here for the first time the localization of β-receptors in the lung by light microscopic autoradiography. Initial biochemical studies showed that 3H-dihydroalprenolol (3H-DHA) bound to slide-mounted frozen sections of ferret lung with the characteristics expected of interaction with β-receptors. Autoradiograms prepared by apposition of dry emulsion-coated coverslips to these sections showed that the distribution of β-receptors in the lung was widespread. The highest concentration of β-receptors was found in smooth muscle of bronchioles with somewhat lower densities in smooth muscle of large airways. Labelling also occurred in airway epithelium, submucosal glands and vascular smooth muscle. Alveolar walls were heavily labelled and as type II pneumocytes, which are known to have β-receptors, comprise only a small portion of the surface area, β-receptors must also be present on type I cells and/or capillary endothelial cells, although their function is at present unknown.

Plasma histamine and catecholamines in stable asthmatic subjects.

Abstract: 1. Venous plasma histamine and catecholamines were measured in stable asthmatic subjects by a recently developed specific and sensitive radioenzymatic assay. 2. Plasma histamine concentrations were significantly elevated in both extrinsic and intrinsic asthmatic subjects, compared with both normal controls and patients with chronic obstructive airways disease. There was no correlation between histamine concentration and severity of airways obstruction, however. 3. Elevated plasma histamine concentrations at rest-5-indicate increased release of mediators from ‘leaky’ mast cells in asthma. 4. Plasma catecholamine concentrations in asthmatic subjects did not differ from normal and there was no correlation with severity of broncho- constriction or with plasma histamine concentration.

Hyperventilation-induced asthma: evidence for two mechanisms.

Abstract: The mechanism by which airway cooling induces airflow obstruction in asthmatic subjects has not yet been established. Using a pair of isocapnic hyperventilation challenges, with a 40-minute interval, we looked for the presence of a refractory period in 19 asthmatic patients (aged 9-18 years). The subjects fell into two groups. The eight in the "non-refractory" group showed less than a 25% reduction in response to the second challenge, but the 11 in the "refractory" group showed at least a 35% reduction. Twelve subjects also performed a hyperventilation challenge after cholinergic blockade with inhaled ipratropium bromide. In five, in whom no refractoriness after hyperventilation was seen, there was a significant protection from cholinergic blockade (p less than 0.05). In these a vagal (cholinergic) reflex seems likely. The remaining seven, who had a refractory period, received no significant protection from cholinergic blockade and therefore no evidence for the presence of any cholinergic mechanism. We conclude that two mechanisms are responsible for hyperventilation-induced asthma, one of which is a vagal reflex while mediator release may be the other.

Circadian variation in adrenergic responses in asthmatic subjects.

Abstract: 1. To determine whether circadian variations in adrenergic responsiveness might underlie nocturnal wheezing in asthma, we measured cardiovascular, airway and plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) responses to stepwise infusions of L-adrenaline (0.01, 0.03 and 0.075 microgram min-1 kg-1) at 4 h intervals over 24 h in five extrinsic asthmatic men. 2. Peak expiratory flow, blood pressure, heart rate and plasma cyclic AMP showed a significant circadian variation with peak values at 16.00 hours and trough values at 04.00 hours. 3. The beta 2-adrenoceptor-mediated increases in peak flow and cyclic AMP were similar at all times, but adrenergic responsiveness (measured by response/log dose of infused adrenaline) was greater at 04.00 hours than at 16.00 hours because of the lower baseline values at night. 4. Blood pressure and heart rate responses to adrenaline infusions did not significantly differ over 24 h. 5. Airway responses to inhaled adrenaline were studied on the second day; the mean peak flow after adrenaline was similar at 16.00 hours to that at 04.00 hours and since the pretreatment values were lower at 04.00 hours, the magnitude of response to inhaled adrenaline was greater at night. 6. We conclude that there is no significant circadian change in adrenergic responses in asthma and that adrenoreceptor dysfunction is not important in the pathogenesis of nocturnal asthma.

The Effects of Almitrine on the Ventilatory Response to Hypoxia and Hypercapnia in Normal Subjects

Abstract: 1. Almitrine at a dose of 0.5 mg h-1 kg-1 given intravenously over 2 h had no effect on resting ventilation in normal males. 2. There was a small, but insignificant, rise in the hypercapnic drive to breathe as compared with placebo. 3. A large rise in the hypoxic drive to breathe was seen in response to almitrine. 4. These findings support the claim that almitrine has its action on ventilation via the peripheral chemoreceptors. 5. No correlation between blood levels of almitrine and the rise in hypoxic response was seen.

Endogenous opiates and the control of breathing in normal subjects and patients with chronic airflow obstruction.

Abstract: To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.

In vivo Identification and Distribution of Alpha- and Beta-Adrenoceptors in Rat Heart and Lung

Abstract: Uptake of 3H-prazosin (3H-PZ), a potent alpha-adrenoceptor antagonist, and 3H-dihydroalprenolol (3H-DHA), a potent beta-antagonist, was measured in rat hear