Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat

Sugihara, Megumi; Morita, Hikaru; Matsuda, Miho; Umebayashi, Hisanori; Kajioka, Shunichi; S, Itó; Nishida, Motohiro; Inoue, Ryosuke; Futatsuki, Toshiko; Yamazaki, Jun; Mori, Yasuo; Inoue, Ryuji; Ito, Yushi; Abe, Kihachiro; Hirata, Masato

doi:10.1254/jphs.10281fp

Cited by 7 publications

(8 citation statements)

References 60 publications

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“…Moreover, UTPinduced contraction appears to be mediated by G-proteincoupled receptors activating PLC, leading to increase in intracellular calcium concentration by release from intracellular stores. The observation that UTP-induced contraction was preserved in low calcium medium and in the presence of nifedipine discarding the possibility that UTP may activate P2X receptor cation channels promoting calcium influx via nifedipine-sensitive calcium channels, as reported in rat vascular muscle [38,39].…”

Section: Discussionmentioning

confidence: 68%

Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum

Zizzo

Mastropaolo

Grählert

et al. 2011

Purinergic Signalling

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We investigated the possible modulation of the intestinal contractility by uracil nucleotides (UTP and UDP), using as model the murine small intestine. Contractile activity of a mouse ileum longitudinal muscle was examined in vitro as changes in isometric tension. Transcripts encoding for uracil-sensitive receptors was investigated by RT-PCR. UDP induced muscular contractions, sensitive to PPADS, suramin, or MRS 2578, P2Y 6 receptor antagonist, and mimicked by PSB 0474, P2Y 6 -receptor agonist. UTP induced biphasic effects characterized by an early inhibition of the spontaneous contractile activity followed by muscular contraction. UTP excitatory effects were antagonized by PPADS, suramin, but not by MRS 2578, whilst the inhibitory effects were antagonized by PPADS but not by suramin or MRS 2578. UTPγS, P2Y 2 / 4 receptor agonist but not 2-thio-UTP, P2Y 2 receptor agonist, mimicked UTP effects. The inhibitory effects induced by UTP was abolished by ATP desensitization and increased by extracellular acidification. UDP or UTP responses were insensitive to TTX, atropine, or L-NAME antagonized by U-73122, inhibitor of phospholipase C (PLC) and preserved in the presence of nifedipine or low Ca 2+ solution.

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Section: Discussionmentioning

confidence: 68%

Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum

Zizzo

Mastropaolo

Grählert

et al. 2011

Purinergic Signalling

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“…Sanchez-Fernandez et al (15) show that UTP causes Ca 2+ mobilization from intracellular stores of culture bovine aortic cells which persisted in the presence of L-type channel blockers or following removal of extracellular Ca 2+ . Sugihara et al (16) reported a dual action of UTP on arterial smooth muscle with contributions from both P2X and P2Y receptor signalling. These authors show that Ca 2+ entry through L-type channels mediate a phasic contraction while Ca 2+ release from endoplasmic reticulum caused tonic contraction of rat aortic rings (16).…”

Section: Discussionmentioning

confidence: 99%

“…Sugihara et al (16) reported a dual action of UTP on arterial smooth muscle with contributions from both P2X and P2Y receptor signalling. These authors show that Ca 2+ entry through L-type channels mediate a phasic contraction while Ca 2+ release from endoplasmic reticulum caused tonic contraction of rat aortic rings (16). …”

Section: Discussionmentioning

confidence: 99%

Ca<sup>2+</sup> dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries

Panhwar

Rainbow

Jackson

et al. 2015

J. Smooth Muscle Res.

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Uridine triphosphate (UTP) can be released from damaged cells to cause vasoconstriction. Although UTP is known to act through P2Y receptors and PLC activation in vascular smooth muscle, the role of PKC in generating the response is somewhat unclear. Here we have used Tat-linked membrane permeable peptide inhibitors of PKC to assess the general role of PKC and also of specific isoforms of PKC in the UTP induced contraction of rat mesenteric artery. We examined the effect of PKC inhibition on UTP induced contraction, increased cytoplasmic Ca2+ and reduction of K+ currents and found that PKC inhibition caused a relatively small attenuation of contraction but had little effect on changes in cytoplasmic Ca2+. UTP attenuation of both voltage-gated (Kv) and ATP-dependent (KATP) K+ currents was abolished when intracellular Ca2+ was decreased from 100 to 20 nM. PKC inhibition reduced slightly the ability of UTP to attenuate Kv currents but had no effect on KATP current inhibition. In conclusion, both UTP induced contraction of mesenteric artery and the inhibition of Kv and KATP currents of mesenteric artery smooth muscle cells by UTP are relatively independent of PKC activation; furthermore, the inhibition of both Kv and KATP currents requires intracellular Ca2+.

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“…Western blot analysis. Western blots were performed as previously described (20). Briefly, cells (AM-1, HaCaT, HSC-3 KD and hOCs) were homogenized in 1 ml ice-cold lysis buffer and centrifuged at 50,000 x g for 30 min at 4˚C.…”

Section: Methodsmentioning

confidence: 99%

“…Specimens were removed surgically from three patients with primary ameloblastoma (plexiform, follicular and basal cell types); all patients provided informed consent before enrollment. Immunohistochemistry was performed as previously described (20). Briefly, following the initial biopsy, all specimens were fixed in 4% PFA in phosphate-buffered saline (pH 7.4) overnight, embedded in paraffin wax and sectioned at 5 µm.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone

Yoshimoto

Morita

Matsubara

et al. 2016

International Journal of Oncology

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Ameloblastoma is the most common benign odontogenic tumor in Japan. It is believed that it expands in the jaw bone through peritumoral activation of osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL) released from the ameloblastoma, as in bone metastases of cancer cells. However, the clinical features of ameloblastoma, including its growth rate and patterns of invasion, are quite different from those of bone metastasis of cancer cells, suggesting that different underlying mechanisms are involved. Therefore, in the present study, we examined the possible mechanisms underlying the invasive expansion of ameloblastoma in the jaw bone. Expression levels of RANKL assessed by western blotting were markedly lower in ameloblastoma (AM-1) cells than in highly metastatic oral squamous cell carcinoma (HSC-3) cells. Experiments coculturing mouse macrophages (RAW264.7) with AM-1 demonstrated low osteoclastogenic activity, as assessed by tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell formation, probably because of low release of RANKL, whereas cocultures of RAW264.7 with HSC-3 cells exhibited very high osteoclastogenic activity. Thus, RANKL release from AM-1 appeared to be too low to generate osteoclasts. However, AM-1 cultured directly on calcium phosphate-coated plates formed resorption pits, and this was inhibited by application of bafilomycin A1. Furthermore, vacuolar-type H+-ATPase (V-ATPase) and H+/Cl- exchange transporter 7 (CLC-7) were detected on the surface of AM-1 cells by plasma membrane biotinylation and immunofluorescence analysis. Immunohistochemical analysis of clinical samples of ameloblastoma also showed plasma membrane-localized V-ATPase and CLC-7 in the epithelium of plexiform, follicular and basal cell types. The demineralization activity of AM-1 was only 1.7% of osteoclasts demineralization activity, and the growth rate was 20% of human normal skin keratinocytes and HSC-3 cells. These results suggest that the slow expansion of several typical types of ameloblastomas in jaw bone is attributable to its slow growth and low demineralization ability.

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Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat

Cited by 7 publications

References 60 publications

Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum

Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum

Ca<sup>2+</sup> dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries

Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone

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