Bombesin stimulates human nasal mucous and serous cell secretion in vivo

1992 ◽  
Vol 262 (1) ◽  
pp. L48-L52 ◽  
Author(s):  
J. N. Baraniuk ◽  
P. B. Silver ◽  
J. D. Lundgren ◽  
P. Cole ◽  
M. A. Kaliner ◽  
...  

Bombesin, gastrin-related peptide (GRP), and related peptides sharing the common carboxyterminal sequence stimulate lactoferrin (serous cell marker) and glycoconjugate (mucous cell and goblet cell marker) release from human nasal mucosal explants in vitro. In vivo, GRP released from trigeminal sensory nerves may act upon GRP-bombesin binding sites on respiratory epithelial cells and submucosal glands. To determine whether GRP-bombesin can stimulate nasal secretion in vivo, bombesin was administered to eight normal subjects by unilateral, topical administration. Secretions from both nostrils were collected for measurement of total protein, lysozyme, hexose-containing glycoconjugates, and albumin (marker of vascular permeability). Baseline secretions contained 72.0 +/- 17.3 micrograms/ml of total protein, 14 +/- 2 micrograms/ml of lysozyme, 113 +/- 44 micrograms/ml of hexose-containing glycoconjugates, and 7.8 +/- 3.4 micrograms/ml of albumin. Hexose-containing glycoconjugate secretion was significantly increased after 1 nmol (385 +/- 63 micrograms/ml, P less than 0.001 by analysis of variance), 10, 100, and 1,000 nmol of bombesin, but the secretion was not dose dependent. Significant lysozyme (24 +/- 3 micrograms/ml, P less than 0.05) and total protein (155 +/- 23 micrograms/ml, P less than 0.01) secretion occurred after 1,000 nmol. No statistically significant changes in albumin secretion occurred at any dose. Saline had no significant effects on secretion. Therefore, bombesin stimulated secretion from submucosal glands and possibly epithelial cells in the human nose without affecting vascular permeability.

1991 ◽  
Vol 71 (3) ◽  
pp. 939-944 ◽  
Author(s):  
B. Davis ◽  
H. C. Tseng

To investigate how central and peripheral nerves affect lysozyme secretion from tracheal submucosal glands in ferrets we injected substance P (20 nmol/kg in 200 microliters) intracisternally or intravenously into anesthetized artificially ventilated ferrets. We collected 3-ml samples from a perfused (3 ml/5 min) segment of trachea in situ during 15 min before and 45 min after injection of substance P. Content of lysozyme, a specific marker of tracheal submucosal gland serous cell secretion in ferrets, was measured spectrophotometrically in each sample. Intracisternal substance P increased peak lysozyme output threefold compared with baseline. This increase was abolished completely by cutting both superior laryngeal nerves (SLN) and was partially inhibited by atropine, phentolamine, or propranolol. Intravenous substance P increased peak lysozyme output 10-fold compared with baseline. This increase was partly abolished by cutting both SLN. We concluded that intracisternal substance P stimulated the central nervous system (CNS) and activated cholinergic, adrenergic, and nonadrenergic noncholinergic secretomotor nerves to tracheal glands and that intravenous substance P increased lysozyme secretion both by acting directly on tracheal glands and indirectly on the CNS to activate secretomotor nerves.


1990 ◽  
Vol 68 (2) ◽  
pp. 726-730 ◽  
Author(s):  
A. M. Price ◽  
S. E. Webber ◽  
J. G. Widdicombe

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.


2019 ◽  
Vol 244 (7) ◽  
pp. 554-564 ◽  
Author(s):  
Ana Klisuric ◽  
Benjamin Thierry ◽  
Ludivine Delon ◽  
Clive A Prestidge ◽  
Rachel J Gibson

M cells are an epithelial cell population found in the follicle-associated epithelium overlying gut-associated lymphoid tissues. They are specialized in the transcytosis of luminal antigens. Their transcytotic capacity and location in an immunocompetent environment has prompted the study of these cells as possible targets for oral drug delivery systems. Currently, the models most commonly used to study M cells are restricted to in vivo experiments conducted in mice, and in vitro studies conducted in models comprised either of primary epithelial cells or established cell lines of murine or human origin. In vitro models of the follicle-associated epithelium can be constructed in several ways. Small intestinal Lgr5+ stem cells can be cultured into a 3D organoid structure where M cells are induced with RANKL administration. Additionally, in vitro models containing an “M cell-like” population can be obtained through co-culturing intestinal epithelial cells with cells of lymphocytic origin to induce the M cell phenotype. The evaluation of the efficiency of the variations of these models and their relevance to the in vivo human system is hampered by the lack of a universal M cell marker. This issue has also hindered the advancement of M cell-specific targeting approaches aimed at improving the bioavailability of orally administered compounds. This critical review discusses the different approaches utilized in the literature to identify M cells, their efficiency, reliability and relevance, in the context of commonly used models of the follicle-associated epithelium. The outcome of this review is a clearly defined and universally recognized criteria for the assessment of the relevance of models of the follicle-associated models currently used. Impact statement The study of M cells, a specialized epithelial cell type found in the follicle-associated epithelium, is hampered by the lack of a universal M cell marker. As such, many studies lack reliable and universally recognized methods to identify M cells in their proposed models. As a result of this it is difficult to ascertain whether the effects observed are due to the presence of M cells or an unaccounted variable. The outcome of this review is the thorough evaluation of the many M cell markers that have been used in the literature thus far and a proposed criterion for the identification of M cells for future publications. This will hopefully lead to an improvement in the quality of future publications in this field.


1993 ◽  
Vol 264 (4) ◽  
pp. L345-L350
Author(s):  
A. Z. Gawin ◽  
J. N. Baraniuk ◽  
J. D. Lundgren ◽  
M. Kaliner

The effects of gastrin-releasing peptide (GRP), bombesin, GRP-(1–16) and GRP-(21–27) on guinea pig nasal mucosal secretion were studied in vivo. GRP, bombesin, and GRP-(21–27) induced significant secretion of total protein, albumin, and alkaline phosphatase. GRP induced significant secretion at lower concentrations (10(-11) and 10(-10) M) than were required for bombesin and GRP-(21–27) (10(-7) M). GRP-(1–16) did not stimulate secretion, indicating that the COOH-terminal region of GRP contained the secretagogic principle. Capsaicin, a stimulant of nociceptive sensory nerves, stimulated GRP release into nasal secretions. These data suggest that GRP is present in guinea pig nasal mucosa and that the COOH-terminal region of GRP may regulate mucosal macromolecule secretion.


1993 ◽  
Vol 75 (2) ◽  
pp. 798-804 ◽  
Author(s):  
A. Z. Gawin ◽  
J. N. Baraniuk ◽  
Y. Igarashi ◽  
M. A. Kaliner

Capsaicin-sensitive mechanisms may contribute to histamine's effects on guinea pig nasal mucosal secretion in vivo. Histamine nasal provocations were performed, secretions were collected, and the following variables were measured: total protein (marker of all secretory processes), alkaline phosphatase (marker of glandular secretion), and albumin (marker of vascular permeability, epithelial permeability, and glandular transport). By challenging only one nostril (ipsilateral), the contralateral responses to these challenges were examined and the nature of "nasonasal" reflexes was determined. Histamine increased albumin and alkaline phosphatase concentrations in lavage fluid on the ipsilateral and contralateral sides. The alkaline phosphatase secretion was reduced by atropine. Capsaicin induced dose-dependent albumin exudation. To determine the roles of capsaicin-sensitive sensory nerves, one nostril was desensitized by topical application of capsaicin to one nostril in increasing doses daily for 5 wk. This led to 1) ablation of all secretory responses to capsaicin, 2) ablation of histamine-induced alkaline phosphatase and total protein secretion, 3) blunted histamine-induced albumin exudation on the desensitized side, and 4) ablation of histamine-induced contralateral reflex-mediated protein secretion. These results indicate that capsaicin stimulates vascular responses, probably by stimulating nociceptive nerve axon responses. Histamine induces vascular responses and albumin exudation by both capsaicin-sensitive sensory neuron axon responses and direct effects on vessels. Histamine stimulates glandular secretion through a capsaicin-sensitive afferent/cholinergic efferent reflex.


Author(s):  
D.L. Luchtel

Most molecules synthesized for extracellular transport are believed to be secreted from the cell by exocytosis. Exocytosis is also generally accepted as the mechanism of mucous cell secretion. We are studying the control of mucous and fluid secretion in a gastropod mollusc, Agriolimax columbianus, and have shown that it is an excellent model for the study of mucous secretions because of the copiousness and precise control of these secretions and the fact that they are released onto an exposed body surface, rather than within body cavities. Our observations of chemically-fixed material (glutaraldehye followed by osmium) showed “omega figures” typical of mucous vesicle exocytosis. On the other hand, in vivo observations showed that membrane-bound vesicles were shed intact from mucous cells.2 As an alternative to chemical fixation, we used a physical method of fixation, ultrarapid freezing, to determine more accurately the ultrastructural basis of mucous cell secretion.Intact body wall of the terrestrial slug, A. columbianus, was frozen with a Cryopress™ (Med-Vac Inc., St. Louis, MO) by slamming the tissue against the face of a polished copper block cooled in liquid N2 The frozen tissue was then freeze-substituted in cold (-80°C) osmium-containing acetone for several days, then brought to room temperature and embedded in Epon. Sections for EM were observed in a JEOL-100S TEM.


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