Contribution of reverse Na<sup>+</sup>–Ca<sup>2+</sup> exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra

Bradley, Eamonn; Hollywood, Mark A.; Johnston, Louise; Large, Roddy J.; Matsuda, Takehisa; Baba, Akemichi; McHale, Noel G.; Thornbury, Keith D.; Sergeant, Gerard P.

doi:10.1113/jphysiol.2006.110932

Cited by 39 publications

(60 citation statements)

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“…gene knock-out models) in order to determine which TRP proteins are functionally involved in the regulation of ASM contraction and airway calibre. [135][136][137][138]. The current authors later showed the importance of this mechanism in SR refilling in bovine ASM [16], as have others in murine ASM [139].…”

Section: +mentioning

confidence: 56%

Ionic mechanisms and Ca2+ handling in airway smooth muscle

Hirota

Helli²,

Janssen³

2007

European Respiratory Journal

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Asthma is a disease characterised by reversible contraction of airway smooth muscle. Many signalling pathways are now known to underlie that contraction, almost all of which revolve around Ca 2+ handling. Ca 2+ homeostasis in turn is governed by a wide variety of ionic mechanisms, which are still poorly understood. The present review will briefly summarise those mechanisms that have been recognised for decades, but will then devote considerable attention to several novel ionic signalling mechanisms such as capacitative Ca 2+ entry, the reverse mode of

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Section: +mentioning

confidence: 56%

Ionic mechanisms and Ca2+ handling in airway smooth muscle

Hirota

Helli²,

Janssen³

2007

European Respiratory Journal

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“…In order to examine the contribution of the NCX, tissues were treated with KB-R7943 (10 or 20 mM), a selective inhibitor of the reverse-mode (i.e. Ca 2+ influx mode) of the NCX [17][18][19][20][21]. Both 10 and 20 mM KB-R7943 significantly reduced successive ACh-induced contractions by ,50% (fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…KB-R7943 is a selective inhibitor of the NCX, and blocks the reverse-mode almost 60 times more strongly than the forward-mode [17][18][19][20][21]. When examining the pharmacology of KB-R7943, BRADLEY et al [18] reported that it had no effect on the release of Ca 2+ from the SR, and nor did it alter the inward current mediated by Ca 2+ -dependent Cl -channels. Furthermore, KAWANO et al [28] reported that high concentrations of KB-R7943 (30-100 mM) reduced spontaneous Ca 2+ oscillations in human mesenchymal stem cells, but had no effect on the lanthanum-sensitive component of these oscillations mediated by NSCCs.…”

Section: Discussionmentioning

confidence: 99%

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Store-refilling involves both L-type calcium channels and reverse-mode sodium calcium exchange in airway smooth muscle

Hirota¹,

Janssen²

2007

European Respiratory Journal

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The aim of the present study was to examine the relative contributions to storerefilling of the two following voltage-regulated calcium ion influx pathways: 1) L-type-Ca 2+ channels; and 2) the reverse-mode of the sodium-calcium exchanger (NCX).Successive acetylcholine-induced contractions, triggered in bovine tracheal smooth muscle strips, were measured to determine the effect of intervention on contractions as an indication of the extent of store-refilling.Pre-treating the tissues with cromakalim significantly reduced the magnitude of successive contractions. Zero-Ca 2+ bathing media abolished the contractions, an effect that was completely reversed upon reintroduction of Ca 2+. Inhibition of L-type Ca 2+ channels, with nifedipine, significantly reduced the magnitude of the contractions. Similarly, inhibition of the reverse-mode of the NCX, with KB-R7943, significantly reduced the magnitude of the contractions. However, neither nifedipine nor KB-R7943 alone reduced contractions to the same extent as observed under zero-Ca 2+ conditions. Concurrent treatment with nifedipine and KB-R7943 almost abolished successive contractions. Furthermore, concurrent treatment with nifedipine and zero-Na + bathing media displayed a significantly greater effect than nifedipine alone. Probing the expression of NCX1 isoforms by Western blotting revealed the presence of three bands of 160, 120 and 110 kDa. The 120-and 110-kDa bands were identified as variably spliced NCX isoforms, NCX1.1 and NCX1.3, respectively. Taken together, these data suggest that influx of calcium ions through both L-type calcium channels and the reverse-mode of the sodium-calcium exchanger is necessary for complete store-refilling in airway smooth muscle.

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“…Theˆgure depicts cellular signal cascades leading to astrocytic apoptosis induced by Ca Z paradox. Excitotoxicity of retinal ganglion cells 14) Neuronal and glial cell death 15,16) Cardiac ischemia 17) Inhibition of cardiac NCX1.1 accompanied by cardiac protection 18 20) Renal re-perfusion injury 13) Ca Z oscillation in Cajal cell of smooth muscle 21) Cardiac Ca Z current 22) Vol. 127 (2007) 46) Nociception Vulnerability to ischemia 47) Brain ischemic damages …”

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confidence: 99%

Molecular Pharmacologic Approaches to Functional Analysis of New Biological Target Molecules for Drug Discovery

Baba

2007

YAKUGAKU ZASSHI

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This review focuses on two pharmacologic approaches to the functional evaluation of new target molecules for drug discovery. One is the development of a novel speciˆc antagonist of the Na ＋ -Ca Z exchanger (NCX) SEA0400. The other is a comprehensive analysis of the functions of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide ligand for G protein-coupled receptors. NCX is the one of the last target molecules regulating the cellular Ca Z concentration. There was no e‹cient way to address the pathophysiologic roles of NCX until a speciˆc antagonist, 2-[4-[(2,5-di‰uorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), was developed. Our recent studies using SEA0400 clearly showed the possible roles of NCX in several pathologic states of cardiovascular and nervous tissues. In our second approach including gene-targeting methods, we found new, unexpected roles of PACAP in higher brain functions, such as psychomotor, cognition, photoentrainment, and nociception. Based on these experimentalˆndings, a genetic association study in schizophrenia patients revealed that the single-nucleotide polymorphisms of the PACAP gene are signiˆcantly associated with the hypofunction of the hippocampus. Regarding the peripheral roles of PACAP, we found that PACAP is involved not only in the regulation of insulin secretion in pancreatic islets, but also in the regulation of islet turnover. In subsequent phenotypic analysis of PACAP transgenic mice, we identiˆed novel candidate genes that probably have promising functional roles.

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Contribution of reverse Na⁺–Ca²⁺ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra

Abstract: Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit regular Ca

Cited by 39 publications

References 36 publications

Ionic mechanisms and Ca2+ handling in airway smooth muscle

Ionic mechanisms and Ca2+ handling in airway smooth muscle

Store-refilling involves both L-type calcium channels and reverse-mode sodium calcium exchange in airway smooth muscle

Molecular Pharmacologic Approaches to Functional Analysis of New Biological Target Molecules for Drug Discovery

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Contribution of reverse Na+–Ca2+ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra

Abstract: Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit regular Ca

Cited by 39 publications

References 36 publications

Ionic mechanisms and Ca2+ handling in airway smooth muscle

Ionic mechanisms and Ca2+ handling in airway smooth muscle

Store-refilling involves both L-type calcium channels and reverse-mode sodium calcium exchange in airway smooth muscle

Molecular Pharmacologic Approaches to Functional Analysis of New Biological Target Molecules for Drug Discovery

Contact Info

Product

Resources

About

Contribution of reverse Na⁺–Ca²⁺ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra