Role of phosphoinositide 3-kinase in the nonselective cation channel activation by endothelin-1/endothelinBreceptor

2003 ◽  
Vol 284 (2) ◽  
pp. C506-C510 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Nobuo Hashimoto ◽  
Tomoh Masaki
Keyword(s):  
Chinese Hamster ◽  
Pi3k Pathway ◽  
Cation Channel ◽  
Channel Blockers ◽  
Nonselective Cation Channel ◽  
Channel Activation ◽  
Endothelin 1 ◽  
Ovarian Cells ◽  
Phosphoinositide 3 Kinase

We recently demonstrated that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channel (designated NSCC-1 and NSCC-2) in Chinese hamster ovarian cells expressing endothelinB receptor (CHO-ETBR). These channels can be discriminated using the Ca2+ channel blockers, LOE 908 and SK&F 96365. LOE 908 is a blocker of NSCC-1 and NSCC-2, whereas SK&F 96365 is a blocker of NSCC-2. In this study, we investigated the possible role of phosphoinositide 3-kinase (PI3K) in the ET-1-induced activation of NSCCs in CHO-ETBR using wortmannin and LY-294002, inhibitors of PI3K. ET-1-induced Ca2+ influx was partially inhibited in CHO-ETBR pretreated with wortmannin or LY-294002. In contrast, addition of wortmannin or LY-294002 after stimulation with ET-1 did not suppress Ca2+ influx. The Ca2+ channels activated by ET-1 in wortmannin- or LY-294002-treated CHO-ETBR were sensitive to LOE 908 and resistant to SK&F 96365. In conclusion, NSCC-2 is stimulated by ET-1 via PI3K-dependent cascade, whereas NSCC-1 is stimulated independently of the PI3K pathway. Moreover, PI3K seems to be required for the initiation of the Ca2+ entry through NSCC-2 but not for its maintenance.

Physiological Role of Ca2+-Permeable Nonselective Cation Channel in Endothelin-1-Induced Contraction of Rabbit Aorta

1997 ◽  
Vol 30 (4) ◽  
pp. 504-509 ◽  
Author(s):  
Taro Komuro ◽  
Soichi Miwa ◽  
Xiao-Feng Zhang ◽  
Tetsuya Minowa ◽  
Taijiro Enoki ◽  
...  
Keyword(s):  
Physiological Role ◽  
Rabbit Aorta ◽  
Cation Channel ◽  
Nonselective Cation Channel ◽  
Endothelin 1

scholarly journals Ca2+ channels activated by endothelin-1 in CHO cells expressing endothelin-A or endothelin-B receptors

2001 ◽  
Vol 281 (5) ◽  
pp. C1676-C1685 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Yasuo Okamoto ◽  
Taijiro Enoki ◽  
Nobuo Hashimoto ◽  
Tomoh Masaki
Keyword(s):  
Cho Cells ◽  
Inositol Phosphates ◽  
Chinese Hamster ◽  
Cell Types ◽  
Channel Blockers ◽  
Nonselective Cation Channel ◽  
Type B ◽  
Endothelin 1 ◽  
Endothelin B ◽  
Ca2 Channels

We compared the Ca2+ channels activated by endothelin-1 (ET-1) in Chinese hamster ovary (CHO) cells stably expressing endothelin type A (ETA) or endothelin type B (ETB) receptors using the Ca2+ channel blockers LOE-908 and SK&F-96365. In both CHO-ETA and CHO-ETB, ET-1 at 0.1 nM activated the Ca2+-permeable nonselective cation channel-1 (NSCC-1), which was sensitive to LOE-908 and resistant to SK&F-96365. ET-1 at 1 nM activated NSCC-2 in addition to NSCC-1; NSCC-2 was sensitive to both LOE-908 and SK&F-96365. ET-1 at 10 nM activated the same channels as 1 nM ET-1 in both cell types, but in CHO-ETA, it additionally activated the store-operated Ca2+ channel (SOCC), which was resistant to LOE-908 and sensitive to SK&F-96365. Up to 1 nM ET-1, the level of the formation of inositol phosphates (IPs) was low and similar in both cell types, but, at 10 nM ET-1, it was far greater in CHO-ETA than in CHO-ETB. These results show that, in CHO-ETAand CHO-ETB, ET-1 up to 10 nM activated the same Ca2+ entry channels: 0.1 nM ET-1 activated NSCC-1, and ET-1 ≥ 1 nM activated NSCC-1 and NSCC-2. Notably, in CHO-ETA, 10 nM ET-1 activated SOCCs because of the higher formation of IPs.

Blockers of platelet-derived growth factor-activated nonselective cation channel inhibit cell proliferation

1992 ◽  
Vol 262 (6) ◽  
pp. C1464-C1470 ◽  
Author(s):  
F. Jung ◽  
S. Selvaraj ◽  
J. J. Gargus
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Single Channel ◽  
Cation Channel ◽  
Platelet Derived Growth Factor ◽  
Flufenamic Acid ◽  
Channel Blockers ◽  
Nonselective Cation Channel ◽  
Channel Activation ◽  
Single Channel Analysis

In serum-deprived G(o)-arrested cells, the addition of serum or growth factors initiates a cascade of events that culminates in DNA synthesis and mitosis. Recently, we showed that in mouse L-M(TK-) fibroblasts a 28-pS nonselective cation channel (NS channel) becomes quiescent at G(o) arrest and rapidly active within seconds of platelet-derived growth factor (PDGF) or serum addition, placing this response very early in the postreceptor signaling cascade. However, lack of specific channel blockers hindered determination of whether channel activation was necessary for mitogenesis. Derivatives of N-phenylanthranilic acid (DCA) have been reported to block a pancreatic nonselective channel. Therefore, using single-channel analysis, we examined the effect of these agents on the L-M(TK-) NS channel. Flufenamic acid and mefenamic acid rapidly produced reversible channel block with an inhibitory constant (Ki) approximately 10 microM. Furthermore, the component of the macroscopic K+ efflux shown to be mediated by the NS channel was blocked with a similar Ki value. DCA effects on cell proliferation were tested by measuring cloning efficiency and growth rate. Both were inhibited over the range of concentration that affected channel activity, and a 50% inhibitory dose of 50-100 microM was determined. This observation further substantiates the hypothesis that NS channel activation forms a necessary component in the transduction of the mitogenic signal from the PDGF receptor.

scholarly journals The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1

2019 ◽  
Vol 12 (581) ◽  
pp. eaau0615 ◽  
Author(s):  
Samuel J. Carpentier ◽  
Minjian Ni ◽  
Jeffrey M. Duggan ◽  
Richard G. James ◽  
Brad T. Cookson ◽  
...  
Keyword(s):  
B Cell ◽  
Yersinia Pseudotuberculosis ◽  
Cell Receptor ◽  
Pi3k Pathway ◽  
Inflammasome Activation ◽  
Interacting Protein ◽  
Caspase 1 ◽  
B Cell Receptor Signaling ◽  
Phosphoinositide 3 Kinase

B cell adaptor for phosphoinositide 3-kinase (PI3K) (BCAP) is a signaling adaptor that activates the PI3K pathway downstream of B cell receptor signaling in B cells and Toll-like receptor (TLR) signaling in macrophages. BCAP binds to the regulatory p85 subunit of class I PI3K and is a large, multidomain protein. We used proteomic analysis to identify other BCAP-interacting proteins in macrophages and found that BCAP specifically associated with the caspase-1 pseudosubstrate inhibitor Flightless-1 and its binding partner leucine-rich repeat flightless-interacting protein 2. Because these proteins inhibit the NLRP3 inflammasome, we investigated the role of BCAP in inflammasome function. Independent of its effects on TLR priming, BCAP inhibited NLRP3- and NLRC4-induced caspase-1 activation, cell death, and IL-1β release from macrophages. Accordingly, caspase-1–dependent clearance of a Yersinia pseudotuberculosis mutant was enhanced in BCAP-deficient mice. Mechanistically, BCAP delayed the recruitment and activation of pro–caspase-1 within the NLRP3/ASC preinflammasome through its association with Flightless-1. Thus, BCAP is a multifunctional signaling adaptor that inhibits key pathogen-sensing pathways in macrophages.

scholarly journals A possible role of Ca2+influx through cation channel in endothelin-1-induced vascular contraction.

1994 ◽  
Vol 64 ◽  
pp. 249
Author(s):  
Taijiro Enoki ◽  
Shigeo Kobayashi ◽  
Soichi Miwa ◽  
Tomoh Masaki
Keyword(s):  
Cation Channel ◽  
Vascular Contraction ◽  
Endothelin 1

scholarly journals Activation of two types of Ca2+-permeable nonselective cation channel by endothelin-1

1998 ◽  
Vol 76 ◽  
pp. 75
Author(s):  
Yasushi Iwamuro ◽  
Soichi Miwa ◽  
Tetsuya Minowa ◽  
Taro Komuro ◽  
Xiao-Feng Zhang ◽  
...  
Keyword(s):  
Cation Channel ◽  
Nonselective Cation Channel ◽  
Endothelin 1
Sign in / Sign up

Export Citation Format

Share Document