The effect of K+ channel openers on submucosal gland function and epithelial transport of the ferret trachea, in vitro

Griffin, Andrew

doi:10.1016/0014-2999(95)00215-7

Cited by 4 publications

(5 citation statements)

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“…Evidence from this study also indicates that the bronchodilator Ro 31-6930, which inhibits bronchoconstriction induced by cholinergic agonists (Gater, Paciorek, McKean, Wilson, Brewster & Waterfall, 1993) and secretagogue-induced lysozyme release from submucosal gland cells (Griffin, 1995), also attenuates Ca2+-activated Cl-currents. The finding that inward currents activated by methacholine or, more directly, by intracellular photorelease of Ca2+ were reduced by Ro 31-6930 suggest that Ca2'-activated Cl-channels may be a target site for this drug.…”

Section: Inhibition Of Ca2+tactivated Currents By Ro 31-6930mentioning

confidence: 67%

“…However, Ro 31-6930 did not produce typical K+ channel opener effects in these cultured cells (Griffin & Scott, 1994). These observations, and the fact that glibenclamide produced modest attenuation of K+ channel opener actions on ferret trachea (Griffin, 1995), suggest that Ro 31-6930 may inhibit lysozyme secretion by acting at an additional site to the K+ channel.…”

Section: Introductionmentioning

confidence: 86%

“…In particular Ro 31-6930 (2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide), levcromakalim (BRL38227) and pinacidil attenuate secretagogue-induced lysozyme secretion from serous cells in an in vitro air-filled ferret trachea preparation (Griffin, 1995). The development of cell culture techniques has enabled access to submucosal gland cells with serous cell properties (Benali, Dupuit, Jacquot, Fuchey, Hinnrasky, Ploton & Puchelle, 1989;Sommerhoff & Finkbeiner, 1990;Tournier, Merten, Meckler, Hinnrasky, Fuchey & Puchelle, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells

Griffin¹,

Newman²,

Scott³

1996

Experimental Physiology

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SUMMARYCultured ovine trachea submucosal gland cells release lysozyme in response to extracellular application of secretagogues, including the muscarinic receptor agonist methacholine (20 /LM).Investigation of the ultrastructure has shown that these cells contain electron-dense cored granules, which differ from the intact tissue, but appear to be released in response to the application of methacholine and can be arrested during exocytosis by the application of tannic acid. The release process appears to be linked to electrophysiological events activated by methacholine. Extracellular application of nmethacholine and intracellular photorelease of Ca2+ from DM-nitrophen evoked similar events suggesting that a rise in intracellular Ca2+ may occur following muscarinic receptor activation. Measurements of the reversal potential Land the inhibitory action of the chloride channel blocker niflumic acid (10),UM) indicated that Ca2+ activated Cl channcl activity underlies these events. Some of the cultured submucosal gl.and cells also rcsponded similarly to intracellular photorelease of inositol 1,4,5-trisphosphate, suggesting a possible link between musc.arinic receptor occupation by agonist, release of calcium from stores, and activation of Ca 2'-activated Cl current. Secretion of lysozyme, methacholine-activated currents and currents evoked by intracellular photorelease of Ca2+ \vere also attenuated by the potent bronchodilator Ro 31-6930

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Section: Inhibition Of Ca2+tactivated Currents By Ro 31-6930mentioning

confidence: 67%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells

Griffin¹,

Newman²,

Scott³

1996

Experimental Physiology

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“…This is consistent with the observation that levcromakalim had no effect on ACh‐ or SP‐induced goblet cell secretion in guinea‐pig trachea in vivo (Kuo et al ., 1992b). However, it is in contrast to the inhibition by levcromakalim and other K ATP channel openers of sustained secretion of lysozyme from submucosal gland serous cells in the in vitro ferret whole trachea preparation (Griffin, 1995). It would be of interest to determine whether different classes of K + channel have a different distribution over serous and mucous gland cells and regulate different aspects of the airway secretory process.…”

Section: Discussionmentioning

confidence: 99%

Neuroregulation of mucus secretion by opioid receptors and K_ATP and BK_Ca channels in ferret trachea in vitro

Ramnarine

Liu

Rogers

1998

British J Pharmacology

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1 Opioid agonists inhibit neurogenic mucus secretion in the airways. The mechanism of the inhibition is unknown but may be via opening of potassium (K + ) channels. We studied the e ect on neurogenic secretion in ferret trachea in vitro of the OP 1 receptor (formerly known as d opioid receptor) agonist [DPen 2,5 ]enkephalin (DPDPE), the OP 2 receptor (formely k) agonist U-50,488H, the OP 3 receptor (formerly m) agonist [D-Ala 2 , N-Me-Phe, Gly-ol 5 ]enkephalin (DAMGO), the ATP-sensitive K + (K ATP ) channel inhibitor glibenclamide, the large conductance calcium activated K + (BK Ca ) channel blocker iberiotoxin, the small conductance K Ca (SK Ca ) channel blocker apamin, the K ATP channel opener levcromakalim, a putative K ATP channel opener RS 91309, and the BK Ca channel opener NS 1619. Secretion was quanti®ed by use of 35 SO 4 as a mucus marker. 2 Electrical stimulation increased tracheal secretion by up to 40 fold above sham-stimulated levels. DAMGO or DPDPE (10 mM each) signi®cantly inhibited neurogenic secretion by 85% and 77%, respectively, e ects which were reversed by naloxone. U-50,488H had no signi®cant inhibitory e ect on neurogenic secretion, and none of the opioids had any e ect on ACh-induced or [Sar 9 ]substance Pinduced secretion. 3 Inhibition of neurogenic secretion by DAMGO or DPDPE was reversed by iberiotoxin (3 mM) but not by either glibenclamide or apamin (0.1 mM each). Iberiotoxin alone did not a ect the neurogenic secretory response. 4 Levcromakalim, RS 91309 or NS 1619 (3 nM ± 3 mM) inhibited neurogenic secretion with maximal inhibitions at 3 mM of 68%, 72% and 96%, respectively. Neither levcromakalim nor RS 91309 at any concentration tested signi®cantly inhibited acetylcholine (ACh)-induced secretion, whereas inhibition (60%) was achieved at the highest concentration of NS 1619, a response which was blocked by iberiotoxin. 5 Inhibition of neurogenic secretion by levcromakalim (3 mM) or RS 91309 (30 nM) was inhibited by glibenclamide but not by iberiotoxin. In contrast, inhibition by NS 1619 (30 nM and 3 mM) was blocked by iberiotoxin but not by glibenclamide. 6 We conclude that, in ferret trachea in vitro, OP 1 or OP 3 opioid receptors inhibit neurogenic mucus secretion at a prejunctional site and that the mechanism of the inhibition is via opening of BK Ca channels. Direct opening of BK Ca channels or K ATP channels also inhibits neurogenic mucus secretion. In addition, opening of BK Ca channels inhibits ACh-evoked secretion of mucus. Drugs which open BK Ca channels may have therapeutic anti-secretory activity in bronchial diseases in which neurogenic mechanisms and mucus hypersecretion are implicated in pathophysiology, for example asthma and chronic bronchitis.

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“…Openers of basolateral K + channels, which stimulate transepithelial Cl -secretion, affect methacholine-induced lysozyme output in ferret trachea [8]. Similarly, prostaglandins that control transepithelial Cl -secretion affect lysozyme output [9].…”

Section: Introductionmentioning

confidence: 98%

CFTR and lysozyme secretion in human airway epithelial cells

Duszyk

2001

Pfl�gers Archiv European Journal of Physiology

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Lysozyme is secreted in large quantities in human airways (10-20 mg/day), where it helps to defend against bacterial and fungal infection. Lysozyme expression is restricted to the serous cells of the submucosal glands, which also express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. It is often assumed that mucus secretion in human airways is coupled to anion secretion through CFTR Cl(-) channels located in the apical membrane. Therefore, a defect in CFTR function could cause abnormal mucus secretion leading to persistent bacterial infection and inflammation of the airways. In this study we measured simultaneous secretion of lysozyme and Cl(-) from human airway epithelial serous cells. Secretion of lysozyme was measured by a turbidimetric assay that relies on the ability of lysozyme to disrupt the wall of the bacterium Micrococcus lysodeikticus, thus causing a fall in the optical density of the sample. Secretion of Cl(-) was measured as short-circuit current in a modified Ussing chamber. Activation of Cl(-) secretion by stimulation of cAMP- or Ca(2+)-dependent pathways caused comparable increases in lysozyme secretion. Similarly, blockers of Cl(-) secretion, such as diphenylamine-2-carboxylate (DPC), also reduced lysozyme secretion. However, while treatment of airway submucosal gland cells with antisense oligonucleotides directed against CFTR reduced Cl(-) secretion, it had no significant effect on the total amount of lysozyme secretion. These results suggest a role for functional CFTR in regulation of lysozyme secretion in human airways.

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The effect of K+ channel openers on submucosal gland function and epithelial transport of the ferret trachea, in vitro

Cited by 4 publications

References 25 publications

Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells

Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells

Neuroregulation of mucus secretion by opioid receptors and K_ATP and BK_Ca channels in ferret trachea in vitro

CFTR and lysozyme secretion in human airway epithelial cells

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The effect of K+ channel openers on submucosal gland function and epithelial transport of the ferret trachea, in vitro

Cited by 4 publications

References 25 publications

Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells

Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells

Neuroregulation of mucus secretion by opioid receptors and KATP and BKCa channels in ferret trachea in vitro

CFTR and lysozyme secretion in human airway epithelial cells

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Neuroregulation of mucus secretion by opioid receptors and K_ATP and BK_Ca channels in ferret trachea in vitro