ATP-induced Cl− secretion with suppressed Na+ absorption in rabbit tracheal epithelium

Iwase, Nobuhisa; Sasaki, Tsukasa; Shimura, Sanae; Yamamoto, Mitsunobu; Suzuki, Satoshi; Shirato, Kunio

doi:10.1016/s0034-5687(96)02516-9

Cited by 39 publications

(36 citation statements)

References 29 publications

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“…In addition, they showed that the ATP and UTP effect could be blocked by buffering changes in intracellular Ca 2ϩ , suggesting that [Ca ϩ ] rather than protein kinase C mediates the purinoceptorinduced inhibition of Na ϩ transport. These studies confirm, in freshly excised human tissues, earlier work that showed inhibition of Na ϩ transport by ATP and UTP in cultured human bronchi from CF and normal subjects (3) and respiratory epithelia from other species (4,5). The Ca 2ϩ dependence of the effect on Na ϩ transport agrees with previous studies of human and porcine airways (3,4).…”

supporting

confidence: 90%

A Dual Role for Purinergic Agonists: Closer to Effective Treatment for Cystic Fibrosis?

Barker

2001

Pediatr Res

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supporting

confidence: 90%

A Dual Role for Purinergic Agonists: Closer to Effective Treatment for Cystic Fibrosis?

Barker

2001

Pediatr Res

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“…Nucleotides in extracellular fluid act as autocrine and paracrine hormones to regulate a variety of physiological processes under normal physiological conditions (1,14,28,37,39). Nucleotides inhibit Na ϩ absorption and stimulate Cl Ϫ secretion across epithelia derived from airway, gastrointestinal, and other tissues (10,17,21,38). Recently, McCoy et al (30) found that nucleotide agonists stimulate Cl Ϫ secretion and inhibit Na ϩ absorption in an inner medullary collecting duct (IMCD) cell line (mIMCD-K2).…”

mentioning

confidence: 99%

Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys

Schwiebert¹,

Wallace

Braunstein³

et al. 2002

American Journal of Physiology-Renal Physiology

117

149

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ATP and its metabolites are potent autocrine agonists that act extracellularly within tissues to affect epithelial function. In polycystic kidneys, renal tubules become dilated and/or encapsulated as cysts, creating abnormal microenvironments for autocrine signaling. Previously, our laboratory has shown that high-nanomolar to micromolar quantities of ATP are released from cell monolayers in vitro and detectable in cyst fluids from microdissected human autosomal dominant polycystic kidney (ADPKD) cysts. Here, we show enhanced ATP release from autosomal recessive polycystic kidney (ARPKD) and ADPKD epithelial cell models. RT-PCR and immunoblotting for P2Y G protein-coupled receptors and P2X purinergic receptor channels show expression of mRNA and/or protein for multiple subtypes from both families. Assays of cytosolic Ca2+concentration and secretory Cl− transport show P2Y and P2X purinergic receptor-mediated stimulation of Cl− secretion via cytosolic Ca2+-dependent signaling. Therefore, we hypothesize that autocrine purinergic signaling may augment detrimentally cyst volume expansion in ADPKD or tubule dilation in ARPKD, accelerating disease progression.

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“…1). The short circuit current response by ATP was similar to that by UTP or ATPγS, and adenosine failed to induce any short circuit current responses, suggesting the presence of P 2U -like receptors in rabbit tracheal epithelium [Iwase et al, 1977]. Extracellular nucleotides have been known to activate P 2U receptors and induce a [Ca 2+ ] i rise due to phospholipid metabolism in airway epithelial cells [Boarder et al, 1995;Lazarowski et al, 1994].…”

Section: Effect Of Extracellular Atp On Ion Transport Across the Epitmentioning

confidence: 83%

“…Extracellular nucleotides have been known to activate P 2U receptors and induce a [Ca 2+ ] i rise due to phospholipid metabolism in airway epithelial cells [Boarder et al, 1995;Lazarowski et al, 1994]. Further, the Ca 2+ ionophore ionomycin mimicked the short circuit current response by ATP, while the calmodulin antagonist W-7 abolished it [Iwase et al, 1977]. Based on these findings it can be deduced that extracellular ATP activated Ca 2+ -dependent Cl -channels or secretion in rabbit tracheal epithelium.…”

Section: Effect Of Extracellular Atp On Ion Transport Across the Epitmentioning

confidence: 84%

“…In an Ussing chamber [Iwase et al, 1977] extracellular ATP induced an increase in Cl -secretion across rabbit tracheal epithelium since the ATP-evoked rise in short circuit current was significantly inhibited by a Cl --channel inhibitor, DPC, and not altered by the Na + -channel blocker amiloride (Fig. 1).…”

Section: Effect Of Extracellular Atp On Ion Transport Across the Epitmentioning

confidence: 97%

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Extracellular ATP regulation of airway secretion

Shimura

2001

Drug Development Research

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Both the superficial epithelium and submucosal glands play a role in airway secretion. Electrophysiological experiments showed that extracellular ATP induced an initial transient increase in Cl -secretion followed by a prolonged inhibition of Na + absorption in rabbit tracheal epithelium, which lacks submucosal glands. The response to ATP was mimicked by UTP or ATPγS in untreated normal epithelium, suggesting a P 2U -type receptor in the epithelium. Meanwhile, in tracheal epithelium from SO 2 -induced bronchitic rabbit ATP induced a prolonged increase in Cl -secretion without a decrease in Na + absorption, which was mimicked by adenosine or isoproterenol (ISP). The alteration in the bronchitic epithelium was shown to result from a newly expressed CFTR by both immunohistological and Northern blot analysis. Patch-clamp experiments showed that ATP induced an initial Cl -current followed by K + current in acinar cells of submucosal glands isolated from feline and human trachea. Although ISP alone or adenosine did not evoke any significant current responses, ISP augmented the ATP-induced Cl -and K + currents. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), mimicked the augmentation by ISP. ATP also induced an increase in [Ca 2+ ] i in acinar cells of submucosal glands, which was augmented by ISP. Mucus glycoprotein (MGP) secretion from isolated submucosal glands was also stimulated by ATP but not by adenosine. The ATP-induced MGP secretion was augmented by ISP. These findings suggest that P 2 -receptor stimulation and the resultant [Ca 2+ ] i -rise induce both electrolyte and MGP secretion, which is enhanced by [cAMP] i -rise in airway submucosal glands. Drug Dev.

show abstract

ATP-induced Cl− secretion with suppressed Na+ absorption in rabbit tracheal epithelium

Cited by 39 publications

References 29 publications

A Dual Role for Purinergic Agonists: Closer to Effective Treatment for Cystic Fibrosis?

A Dual Role for Purinergic Agonists: Closer to Effective Treatment for Cystic Fibrosis?

Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys

Extracellular ATP regulation of airway secretion

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