Stimulation by carbachol of mucus gel thickness in rat stomach involves nitric oxide

Price, Kenneth J.; Hanson, Peter J.; Whittle, Brendan J.R.

doi:10.1016/0014-2999(94)90542-8

Cited by 31 publications

(27 citation statements)

References 7 publications

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“…This study did not resolve whether CCh's luminal actions were direct (via receptors on mucosal cells or cholinergic axons) or indirect (via receptors on mucosal noncholinergic axons). However, in vivo actions of luminal cholinergic agents have been reported: luminal CCh stimulated gastric mucus release (69); oral administration of CCh induced cholinergic symptoms (72); and luminal pilocarpin altered intestinal transmucosal potential difference (16). The lack of observed responses to luminally applied CCh in vitro (32) may be explained by dysfunction of the severed mucosal axon plexuses under in vitro experimental conditions.…”

Section: Carbachol-induced Membrane Traffickingmentioning

confidence: 98%

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Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine

Jakab

Collaco

Ameen

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

117

121

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We examined the cell-specific subcellular expression patterns for sodium- and potassium-coupled chloride (NaK2Cl) cotransporter 1 (NKCC1), Na+bicarbonate cotransporter (NBCe1), cystic fibrosis transmembrane conductance regulator (CFTR), and Na+/H+exchanger 3 (NHE3) to understand the functional plasticity and synchronization of ion transport functions along the crypt-villus axis and its relevance to intestinal disease. In the unstimulated intestine, all small intestinal villus enterocytes coexpressed apical CFTR and NHE3, basolateral NBCe1, and mostly intracellular NKCC1. All (crypt and villus) goblet cells strongly expressed basolateral NKCC1 (at approximately three-fold higher levels than villus enterocytes), but no CFTR, NBCe1, or NHE3. Lower crypt cells coexpressed apical CFTR and basolateral NKCC1, but no NHE3 or NBCe1 (except NBCe1-expressing proximal colonic crypts). CFTR, NBCe1, and NKCC1 colocalized with markers of early and recycling endosomes, implicating endocytic recycling in cell-specific anion transport. Brunner's glands of the proximal duodenum coexpressed high levels of apical/subapical CFTR and basolateral NKCC1, but very low levels of NBCe1, consistent with secretion of Cl−-enriched fluid into the crypt. The cholinergic agonist carbachol rapidly (within 10 min) reduced cell volume along the entire crypt/villus axis and promoted NHE3 internalization into early endosomes. In contrast, carbachol induced membrane recruitment of NKCC1 and CFTR in all crypt and villus enterocytes, NKCC1 in all goblet cells, and NBCe1 in all villus enterocytes. These observations support regulated vesicle traffic in Cl−secretion by goblet cells and Cl−and HCO3−secretion by villus enterocytes during the transient phase of cholinergic stimulation. Overall, the carbachol-induced membrane trafficking profile of the four ion transporters supports functional plasticity of the small intestinal villus epithelium that enables it to conduct both absorptive and secretory functions.

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Section: Carbachol-induced Membrane Traffickingmentioning

confidence: 98%

“…Stimulation of the cholinergic gastrointestinal parasympathetic nervous system produces fluid, electrolyte, and mucus secretion (43,69). We used the cholinergic agonist CCh to examine its effect on the subcellular distribution of the four ion transporters (Figs.…”

Section: Carbachol-induced Redistribution Of Nhe3 Cftr Nbce1 and Nmentioning

confidence: 99%

Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine

Jakab

Collaco

Ameen

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

117

121

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“…The first two groups mentioned above studied isolated cell preparations making it very difficult to draw parallels between such systems and whole tissue with its surrounding influences as in our system. However, Brown et al (1992) and Price et al (1994) studied NO-induced increases in mucus gel thickness in rat gut in vivo and concluded that NO was involved in the pathway by which a muscarinic acetylcholine receptor agonist (carbacol) stimulates mucus secretion. We found L-NMMA and the NO donor FK409 to be without effect on ACh-induced mucus secretion indicating that NO plays no role in muscarinic agonist-induced secretion in ferret trachea.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, NO is the dominant non-adrenergic, non-cholinergic (NANC) neurotransmitter of airway bronchodilator nerves (Lei et al, 1993;Belvisi et al, 1995), as well as being a regulator of pulmonary blood flow (Barnes & Liu, 1995), bronchial plasma exudation (Erjefalt et al, 1994), and airway ciliary beat frequency (Jain et al, 1993). In rat stomach NO donors increase mucus gel thickness (Brown et al, 1992), an effector role that may be linked to cholinergic activation of gastric mucus secretion (Price et al, 1994). However, the role of NO in control of secretion of airway mucus, and in particular on neurogenic mucus secretion, remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide inhibition of basal and neurogenic mucus secretion in ferret trachea in vitro

Ramnarine

Khawaja

Barnes

et al. 1996

British J Pharmacology

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1 In order to examine the role of nitric oxide (NO) on airway mucus secretion we studied the effects of the nitric oxide synthase (NOS) inhibitor L-N0-monomethyl-L-arginine (L-NMMA), a novel nitric oxide donor, (± )-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), and the NO precursor Larginine on basal mucus secretion in the ferret trachea in vitro in Ussing chambers. We also determined the effects of these agents upon secretion induced by electrical stimulation of nerves or by acetylcholine (ACh). We used 35SO4 as a mucus marker. 2 L-NMMA (0.01-1 mM) increased basal output of 35SO4-labelled macromolecules with a maximal increase above baseline of 248% at 0.1 mM L-NMMA. L-Arginine (1 mM) alone had no significant effect on basal secretion but reversed the potentiating effect of L-NMMA on basal secretion. L-NMMAinduced increases in basal mucus secretion were sustained for at least 30 min in the continuing presence of the NOS inhibitor. In contrast to the potentiating effects of L-NMMA, FK409 (100 nM) reduced basal secretion by 60% (at 1 nM and at 10 nM it was without effect). 3 Electrical stimulation (50 V, 10 Hz, 0.5 ms for 5 min) increased 35SO4 output by 174%. L-NMMA (1 and 10 mM) present during stimulation of tracheal segments resulted in significant potentiations of 214% and 116%, respectively, of the neurogenic response. The potentiated response to 10 mM L-NMMA was reversed by L-arginine (1 mM). At this dose L-arginine had no effect itself on basal secretion. In contrast to the potentiating effects of L-NMMA on neurogenic secretion, FK409 at 10 nm and 100 nM inhibited the neurogenic response by 98% and 99%. 4 At all concentrations tested, neither L-NMMA (0.01 mM-1 mM) nor FK409 (1-100 mM) had any significant effect on ACh-induced mucus secretion. 5 These observations lead us to conclude that nitric oxide, derived from constitutive NO synthase, acts as an endogenous inhibitor of both basal and neurogenic mucus secretion in ferret trachea in vitro.

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“…Mucus secretion is increased by luminal acid (19,33) and the neuro-and inflammatory mediators acetylcholine and interleukin-1 (8), vasoactive intestinal polypeptide (15), secretin (16,19), and guanylin (10) in duodenum. In the stomach and intestine, mucus secretion and gel thickness are increased by prostaglandins (5,20,24,36), pentagastrin (26,45), carbachol (30,31), nitric oxide (7,30), bradykinin (41) and phorbol esters (29). Of these factors, prostaglandins, products of the cyclooxygenase (COX) pathway, are of paramount clinical importance, because COX inhibition is an important cause of clinical duodenal ulceration (38).…”

mentioning

confidence: 99%

Dynamic regulation of mucus gel thickness in rat duodenum

Akiba¹,

Guth²,

Engel³

et al. 2000

Gastroenterology

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Stimulation by carbachol of mucus gel thickness in rat stomach involves nitric oxide

Cited by 31 publications

References 7 publications

Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine

Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine

Nitric oxide inhibition of basal and neurogenic mucus secretion in ferret trachea in vitro

Dynamic regulation of mucus gel thickness in rat duodenum

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