Search PubMed⌕ Search

Biomedical subjects

R J Phipps

Publications and source records attributed to R J Phipps.

At least 37 records · Page 2Linked to original sources
PubMed1984

Control of mucoglycoprotein output from the rabbit nose.

A method for the collection of rabbit nasal washings to analyse outputs of mucous glycoproteins is described. The radiolabels sodium [35S]sulphate and [3H]glucose are bound to the glycoproteins. The release of bound 35S and 3H was enhanced by cervical sympathetic nerve stimulation. Adrenoceptor agonists (phenylephrine, dobutamine and salbutamol) given I.V. increased the output of 35S, and the last two drugs increased the output of 3H. The blocking effects of thymoxamine and propranolol on these responses are described. Pilocarpine (given I.V. or intranasally) produced large increases in 35S release; histamine had little effect. Irritants (ammonia and cigarette smoke) and diluted serum or plasma, given intranasally, produced large increases in 3H output, and sometimes enhanced 35S release. Radiolabelled nasal washings fractionated on Sepharose CL-4B gel chromatography columns formed two peaks, with most of the radioactivity in the high molecular weight (mucous glycoprotein) peak.

Adrenergic beta-Agonists↗
PubMed1984

A preparation for the study of secretory function of the human bronchus in vitro.

Bronchi, not involved in tumor, were removed from resected human lungs. They were mounted in Ussing chambers containing Krebs-Henseleit solution with radiolabelled precursors of mucus. Airway was examined by both light and electron microscopy. Tissues recently removed from resected lungs exhibited both intra- and extra-cellular oedema and hypoxic changes in mitochondria, but tight junctions between epithelial cells appeared intact, indicating an effective epithelial barrier. Tissues removed from Ussing chambers after up to 6 h showed little oedema and their mitochondria were normal. Their appearance had returned to that of specimens taken that biopsy and fixed immediately. Autoradiographs of specimens from Ussing chambers showed that the mucus-producing cells had concentrated the radiolabels . Mucus in gland ducts was also radiolabelled. Damaged areas of mucous membrane were rare and probably pre-operative. We conclude that resected bronchi, suspended in Ussing chambers, have a structure and secretory activity suitable for investigations of the control of secretion.

Autoradiography↗
PubMed1983

Antigen stimulates glycoprotein secretion and alters ion fluxes in sheep trachea.

We studied the effects of in vitro challenge with specific antigen (Ascaris suum antigen) on glycoprotein secretion and ion fluxes in tracheal tissues from allergic sheep. We mounted tissues in Perspex chambers and measured secretion of 35S- and 3H-labeled glycoproteins and fluxes of Cl- and Na+. In tissues from allergic sheep, A. suum antigen (25 micrograms protein X ml-1) increased glycoprotein secretion. A. suum antigen initially reversed net Cl- flux, causing net absorption of Cl- and of Na+. This was followed 15-30 min later by net secretion of Cl- and of Na+. Pretreatment of tissues with cromolyn (10(-4) M) greatly reduced the effects of A. suum antigen but did not abolish them. The cromolyn-resistant effects were nonspecific, because they were similar to those of in vitro challenges with nonspecific proteins, ovalbumin and ragweed in allergic sheep, and A. suum antigen in nonallergic sheep. We conclude that challenge with A. suum antigen results in mucus hypersecretion in airways of allergic sheep, by both specific and smaller nonspecific effects. Specific effects (cromolyn sensitive) are produced by mediators which are released from airway cells in response to A. suum challenge.

Animals↗
PubMed1982

Sympathomimetic drugs stimulate the output of secretory glycoproteins from human bronchi in vitro.

1. We describe a method for supporting pieces of human bronchi in Ussing chambers, for radiolabelling the contents of the secretory cells with 35S, and for collecting radiolabelled macromolecules secreted on to the luminal aspect of the tissue. This method has previously been used to study airway secretions in animals [R. J. Phipps, J. A. Nadel & B. Davis, American Review of Respiratory Disease, (1980) 121, 359-365]. Evidence is given that the radiolabelled molecules are secretory glycoproteins, probably mucus glycoproteins. 2. Phenylephrine, an alpha-adrenoceptor agonist, increased the rate at which the bronchi secreted radiolabelled glycoproteins. Thymoxamine, an alpha-adrenoceptor antagonist, blocked this effect but propranolol, a beta-adrenoceptor antagonist, did not. 3. Dobutamine, a beta-adrenoceptor agonist, increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this but thymoxamine did not. 4. Salbutamol, a beta 2-adrenoceptor agonist, also increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this effect. 5. We conclude that both alpha- and beta- adrenoceptor agonists increase the rate of glycoprotein secretion in human bronchi in vitro and that this almost certainly means that they increase the rate of mucus secretion.

Autoradiography↗
PubMed1980

Effect of alpha-adrenergic stimulation on mucus secretion and on ion transport in cat trachea in vitro.

In cat trachea mounted in Ussing chambers, we studied the effects of an alpha-adrenergic agonist on mucus secretion measured with 35S bound to sulfated glycoproteins, and on fluxes of Na+ and Cl- ions measured with 22Na and 36Cl, under open-circuit conditions. Phenylephrine (10(-5) M), increased bound 35S-secretion by 147 +/- 24% (mean +/- SE, n = 13), increased JCl-S yields L from 2.54 +/- 0.23 to 7.40 +/- 1.19 microEq/cm2/h (n = 6), and increased JNaS yields L from 1.75 +/- 0.36 to 7.25 +/- 1.10 microEq/cm2/h (n = 6), it decreased 4Cl--L yields S from 2.69 +/- 0.41 to 2.46 +/- 0.41 microEq/cm2/h, but did not change JNa+L yields S. The stimulatory effects of (10(-5) M) phenylephrine were prevented by (10(-5) M) phentolamine, but were unaffected by (10(-5) M) propranolol. In contrast, (10(-5) M) terbutaline, a beta 2-adrenergic agonist, only increased bound 35S secretion by 43 +/- 7% (n = 22) and only increased JCl-S yields L from 3.76 +/- 0.46 to 4.55 +/- 0.41 microEq/cm2/h (n = 6); it did not change the other fluxes. These findings indicate that alpha-adrenergic stimulation causes secretion of sulfated glycoproteins and ion-mediated movement of water into the cat trachea.

Adrenergic alpha-Agonists↗
PubMed1979

Control of mucus secretion and ion transport in airways.

The output of secretions from the airway submucosal glands is regulated by vagal efferent nerves. Stimulation of cough receptors increases mucus output reflexly via the vagus nerves. Adrenergic agonists increase submucosal gland secretions in some species, which indicates that adrenergic receptors are present in these cells. However, evidence for adrenergic nervous pathways to the glands is limited. Irritants and drugs stimulate secretion from epithelial cells by direct effects. There is also evidence that the secretion of epithelial cells can be stimulated by parasympathetic nervous pathways in birds but not in mammals. Active ion transport of Cl- toward the lumen and of Na+ toward the submucosa results in net ion movement toward the airway lumen in unstimulated tracheal epithelia. Drugs and mediators increase the net movement of ions toward the lumen. No agents have yet been found that increase net ion movement toward the submucosa. The link between ion transport and water secretion in airway epithelia, although speculative, seems likely in view of the evidence from other epithelia. Since airway epithelium is a "tight junction" epithelium, modification of the tight junction may alter the transepithelial movement of water and ions. We suggest that the depth and consistency of the periciliary layer of airway secretions determine the ability of the cilia to propel the mucoprotein gel and thereby modify mucociliary transport. To achieve this, secretion of mucus must be controlled separately from the secretion of water. Studies are needed to determine which of the specialized functions of the epithelial cells interact to regulate the clearance of secretions from the airway. Is the sol maintained by secretion and reabsorption of fluid across the epithelium? Does the sol move with the gel by ciliary action or does it remain stationary? Do changes in the epithelial tight junctions influence net water movement and thus indirectly alter the depth of the sol layer? To answer these questions, techniques are needed to study subunits of the airway, including isolated surface cells and submucosal glands; and sensitive methods are required to analyze the very small samples of secretions for glycoprotein and electrolyte content. Intracellular measurements of electrolyte concentrations and electrical potentials may help to elucidate the mechanisms of transepithelial ion and water movement. The control system for the production and removal of respiratory tract secretions may be altered in disease. For instance, chronic stimulation of cough receptors causes reflex secretion and may be the cause of the hyperplasia of submucosal glands and of the abnormal secretions that occur in chronic bronchitis and asthma (50, 58). The abnormally viscid mucus in cystic fibrosis may be due to a defect in Cl- transport, which provides too little water for both the gel and sol layers. These speculations are intended to identify areas for further research, which hopefully will reduce the morbidity and mortality in these common lung diseases.

Animals↗
PubMed1978

The roles of mediators, irritants and allergens in causing mucin secretion from the trachea.

Two species, the cat and the goose, have been investigated to determine whether a variety of pharmacological mediators, irritants and allergens change the rate at which mucins (mucus glycoproteins) are secreted into the trachea. Mucins were labelled by the administration of radioactive precursors which the mucous cells took up and incorporated into glycoproteins. These were periodically washed out of a segment of trachea with physiological saline solution. Changes in the amount of mucin secreted were estimated from measurements of the amount of bound radioactivity in tracheal washings. Histamine increased mucin secretion but the effects were stronger and more consistent in the goose than in the cat. A variety of prostaglandins increased the secretion in both species. 5-Hydroxytryptamine failed to stimulate mucin output in the cat. Ammonia and cigarette smoke both increased mucin secretion in the cat and preliminary results suggest that this was by a combination of local and reflex mechanisms. O-Chlorobenzilidine malononitrile increased secretion from the goose trachea entirely by a local mechanism. Preliminary experiments in which sensitized cats were challenged by various routes have equivocal results on whether anaphylaxis increases airway mucin secretion. It is concluded that irritants cause mucin secretion both by reflexes and local mechanisms. The mechanisms for the latter may well include release of pharmacological mediators.

Allergens↗
PubMed1976

The effects of irritation at various levels of the airway upon tracheal mucus secretion in the cat.

1. Sulphated glycoprotein output from the trachea, isolated in situ, has been measured in anaesthetized cats by a radio-isotopic method. The effects of irritation of various parts of the airway on this mucus output were studied. 2. Mechanical stimulation of the nose and nasopharynx increased tracheal mucus output by reflexes which involved parasympathetic and probably also sympathetic motor pathways. 3. Laryngeal stimulation had a similar through the same motor pathways. 4. Inhalation of ammonia vapour into the lower airways reflexly increased mucus output from the isolated trachea. The efferent pathway for this reflex was mainly or entirely parasympathetic. It is argued that the afferent pathway involved cough receptors. 5. Lung inflation, inhalation of histamine aerosol and intravenous injection of phenyl diguanide (which excite mainly lung stretch receptors, lung 'irritant' receptors and alveolar 'J-receptors' respectively) had no consistent effect on tracheal mucus secretion. 6. The afferent and efferent pathways of these reflexes are discussed.

Afferent Pathways↗