Neural control of goblet cell secretion in guinea pig airways

Tokuyama, Kenichi; Kuo, Han‐Pin; Rohde, J. A. L.; Barnes, Peter J.; Rogers, Duncan F.

doi:10.1152/ajplung.1990.259.2.l108

Cited by 57 publications

(39 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our present study showed that vagal stimulation-induced goblet cell secretion was partly inhibited by the ganglionic blocker hexamethonium with the remaining hexamethonium-resistant part of the response inhibited by capsaicin pretreatment, which suggests that capsaicin-sensitive sensory nerves as well as cholinergic or adrenergic nerves were involved in the secretory response. These results are consistent with our previous study which showed that electrical stimulation of the cervical vagus nerves provokes airway goblet cell discharge by activating cholinergic and capsaicin-sensitive sensory nerves (Tokuyama et al, 1990). Therefore, morphine might have inhibitory effect on both components.…”

Section: Discussionsupporting

confidence: 93%

“…Recently we have demonstrated that airway goblet cells are under neural control. Electrical stimulation of the cervical vagus nerves provokes a significant increase in goblet cell secretion partly via activation of cholinergic nerves and partly via capsaicin-sensitive sensory nerves (Tokuyama et al, 1990). Acute injection of capsaicin, which activates sensory nerve endings to release tachykinins, was also demonstrated to cause goblet cell discharge (Kuo et al, 1990a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically‐induced goblet cell secretion in guinea‐pig trachea

Kuo

Rohde

Barnes

et al. 1992

British J Pharmacology

View full text Add to dashboard Cite

1 Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. 2 Morphine, 1 mg kg-1, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin-sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin-induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. Pen2, D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than DAMGO. A K-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1-pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. 4 DAMGO dose-dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 x 10-7mol kg-'. Neither DPDPE nor U-50,488H had any significant inhibitory effect.The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO. 5 We conclude that opioids inhibit neurally-mediated goblet cell secretion via actions at prejunctional band p-receptors on cholinergic nerves and at p-receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically‐induced goblet cell secretion in guinea‐pig trachea

Kuo

Rohde

Barnes

et al. 1992

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Regulation of ion transport and mucus secretion in the airway mediated by autonomic activity has been previously reported; excitation of parasympathetic nerves increases mucus secretion from goblet cells (30) and also induces fluid secretion through epithelial cells in the central airway apparently by generating a transepithelial potential difference (29). Cholinergic antagonists like atropine are, therefore, commonly prescribed to relieve symptoms of excess secretion/sputum production, prior to endoscopy, or as palliative care for terminally ill patients with lungs flooded with sputum.…”

Section: Discussionmentioning

confidence: 99%

Cholinergic regulation of epithelial sodium channels in rat alveolar type 2 epithelial cells

Takemura

Helms

Eaton

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

We and others have shown that epithelial Na ϩ channels (ENaC) in alveolar type 2 (AT2) cells are activated by ␤2 agonists, steroid hormones, elevated oxygen tension, and by dopamine. Although acetylcholine receptors (AChRs) have been previously described in the lung, there are few reports of whether cholinergic agonists alter sodium transport in the alveolar epithelium. Therefore, we investigated how cholinergic receptors regulate ENaC activity in primary cultures of rat AT2 cells using cell-attached patchclamp recordings to assess ENaC activity. We found that the muscarinic agonists, carbachol (CCh) and oxotremorine, activated ENaC in a dose-dependent manner but that nicotine did not. CCh-induced activation of ENaC was blocked by atropine. Western blotting and immunohistochemistry suggested that muscarinic M2 and M3 receptors (mAChRs) but not nicotinic receptors were present in AT2 cells. Endogenous RhoA and GTP-RhoA increased in response to CCh and the increase was reduced by pretreatment with atropine. We showed that Y-27632, an inhibitor of Rho-associated protein kinase (ROCK), abolished endogenous ENaC activity and inhibited the activation of ENaC by CCh. We also showed that ROCK signaling was necessary for ENaC stability in 2F3 cells, a model for AT2 cells. Our results showed that muscarinic agonists activated ENaC in rat AT2 cells through M2 and/or M3 mAChRs probably via a RhoA/ROCK signaling pathway.

show abstract

“…In the guinea-pig trachea, goblet cells are under autonomic control [26]. However, this is probably not the case in humans and most other mammalian species, in which goblet cells discharge only in response to local irritation [21,27].…”

Section: Goblet Cell Dischargementioning

confidence: 99%

Regulation of depth and composition of airway surface liquid

Widdicombe¹,

Bastacky²,

Wu³

et al. 1997

Eur Respir J

View full text Add to dashboard Cite

R Re eg gu ul la at ti io on n o of f d de ep pt th h a an nd d c co om mp po os si it ti io on n o of f a ai ir rw wa ay y s su ur rf fa ac ce e l li iq qu ui id dThe airways are lined with a film of fluid, which is 5-20 µm deep in healthy individuals. This fluid is believed to consist of two phases [1]. A watery fluid of low viscosity, the "periciliary sol" surrounds the cilia. Above this lies a viscous mucous gel. The cilia are able to beat in the sol. Their tips contact the underside of the mucous blanket and propel it towards the mouth. This system of "mucociliary clearance" serves to remove particles trapped in the mucous gel. The concept of two layers of airway surface liquid (ASL) has been supported by a variety of microscopy studies [2][3][4][5] (fig. 1).Factors influencing the liquid content of sol and gel have been identified but their relative contributions are imperfectly understood. Water will move into the airway lumen in response to active Cl -secretion across the epithelia of the tracheal surface and of submucosal glands. Active absorption of Na + across the surface epithelium serves to remove liquid. These active ion transport processes move liquid by generating local osmotic gradients across the epithelium [6]. Hydrostatic pressure gradients across the epithelium, and differences in osmotic pressure between the media bathing the epithelium's two surfaces, will also influence the net movement of liquid into or out of the lumen. Evaporation is an important factor in the upper airways. Finally, forces of surface tension generated by the closely packed cilia SERIES "AIRWAY MUCUS" Edited by P.K. JefferyNumber 6 in this Series may serve to hold liquid in the airway lumen [7]. These factors are considered in turn below. Additionally, we describe recent experiments in which we have used lowtemperature scanning electron microscope (LT-SEM) to determine the depth and composition of the airway surface liquid (ASL). Gland secretionThe adult human trachea has about 10 submucosal gland openings per mm 2 of airway surface [8]. It is unknown how the structure and numbers of glands change down the airways, except that bronchi have glands, whereas bronchioles do not [9]. In each gland, a ciliated duct leads from the airway surface to an expanded collecting duct into which empty ~10 secretory tubules, each with multiple branches ending in closed acini [10]. The acini are lined by serous cells, the tubules by mucous cells [11]. It is believed that the serous cells secrete fluid which serves to flush out mucins released by the more proximal mucous cells [12]. Consistent with this hypothesis, gland serous cells contain much the highest levels of the cystic fibrosis transmembrane conductance regulator of any cell type in the airways [13] Respir J 1997; 10: 1914-1917

show abstract

Neural control of goblet cell secretion in guinea pig airways

Cited by 57 publications

References 0 publications

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically‐induced goblet cell secretion in guinea‐pig trachea

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically‐induced goblet cell secretion in guinea‐pig trachea

Cholinergic regulation of epithelial sodium channels in rat alveolar type 2 epithelial cells

Regulation of depth and composition of airway surface liquid

Contact Info

Product

Resources

About