Inhibition of neural phospholipase D activity by aminoglycoside antibiotics

Liscovitch, Mordechai; Chalifa, Vered; Danin, Michal; Eli, Yona

doi:10.1042/bj2790319

Cited by 54 publications

(25 citation statements)

References 11 publications

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“…Moreover, the nonselective inhibitor of PLC and phospholipase D, neomycin, had no effect on the responses to PE (Fig. 12B) (Liscovitch et al, 1991). Likewise, although treatment of the cells with 40 M AACOCF 3 , a phospholipase A 2 (PLA 2 ) inhibitor, significantly reduced the response to PE, an alternative PLA 2 inhibitor, MAFP (25 M), had no effect (Fig.…”

Section: Resultsmentioning

confidence: 96%

Evidence for a Novel K⁺Channel Modulated by α_1A-Adrenoceptors in Cardiac Myocytes

Choisy

Hancox²,

Arberry³

et al. 2004

Mol Pharmacol

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Accumulating evidence suggests that steady-state K ϩ currents modulate excitability and action potential duration, particularly in cardiac cell types with relatively abbreviated action potential plateau phases. Despite representing potential drug targets, at present these currents and their modulation are comparatively poorly characterized. Therefore, we investigated the effects of phenylephrine [PE; an ␣ 1 -adrenoceptor (␣ 1 -AR) agonist] on a sustained outward K ϩ current in rat ventricular myocytes. Under K ϩ current-selective conditions at 35°C and whole-cell patch clamp, membrane depolarization elicited transient (I t ) and steady-state (I ss ) outward current components. PE (10 M) significantly decreased I ss amplitude, without significant effect on I t . Preferential modulation of I ss by PE was confirmed by intracellular application of the voltage-gated K ϩ channel blocker tetraethylammonium, which largely inhibited I t without affecting the PE-sensitive current (I ss,PE ). I ss,PE had the properties of an outwardly rectifying steady-state K ϩ -selective conductance. Acidification of the external solution or externally applied BaCl 2 or quinidine strongly inhibited I ss,PE . However, I ss,PE was not abolished by anandamide, ruthenium red, or zinc, inhibitors of TASK acid-sensitive background K ϩ channels. Furthermore, the PE-sensitive current was partially inhibited by external administration of high concentrations of tetraethylammonium and 4-aminopyridine, which are voltage-gated K ϩ channel-blockers. Power spectrum analysis of I ss,PE yielded a large unitary conductance of 78 pS. I ss,PE resulted from PE activation of the ␣ 1A -AR subtype, involved a pertussis toxininsensitive G-protein, and was independent of cytosolic Ca 2ϩ . These results collectively demonstrate that ␣ 1A -AR activation results in the inhibition of an outwardly rectifying steady-state K ϩ current with properties distinct from previously characterized cardiac K ϩ channels.The exceptional diversity of K ϩ channels has particular significance in the heart, where different currents contribute to distinct phases of the cardiac action potential (Snyders, 1999). Steady-state, or plateau, currents show very rapid activation and relatively slow or no inactivation and thereby contribute outward current through out phases 1 and 2, and for the early part of phase 3 of the action potential. They are therefore thought to be of particular importance in cardiac cell types with relatively abbreviated plateau phases (Nattel et al., 1999;Snyders, 1999). However, compared with the transient outward (I to1 ) and delayed rectifier (I K ) K ϩ currents, little is known about the steady-state currents and their modulation (Nattel et al., 1999;Snyders, 1999).The steady-state currents represent a diverse family that includes the so-called ultra-rapid delayed rectifiers (I Kur ) of mouse ventricular myocytes and human and canine atrial myocytes (Nattel et al., 1999). Although I Kur are themselves molecularly diverse, in that they are composed of Kv1.2...

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Section: Resultsmentioning

confidence: 96%

Evidence for a Novel K⁺Channel Modulated by α_1A-Adrenoceptors in Cardiac Myocytes

Choisy

Hancox²,

Arberry³

et al. 2004

Mol Pharmacol

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“…It can serve as a nonspecific phospholipase C inhibitor (13,31) and can block voltage-sensitive Ca 2ϩ channels without affecting the Na ϩ -Ca 2ϩ antiporter (6). Neomycin affects Ca 2ϩ release and inositol phospholipid turnover by inhibiting phosphoinositide kinase (37,44) and also inhibits the activity of phosphatidylcholinephospholipase D (23). Neomycin markedly reduced the cytoplasmic Ca 2ϩ content and inhibited cercosporin production.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Calcium/Calmodulin Signaling in Cercosporin Toxin Biosynthesis byCercosporanicotianae

Chung

2003

Appl Environ Microbiol

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Cercosporin is a non-host-selective, perylenequinone toxin produced by many phytopathogenic Cercospora species. The involvement of Ca 2؉ /calmodulin (CaM) signaling in cercosporin biosynthesis was investigated by using pharmacological inhibitors. The results suggest that maintaining endogenous Ca 2؉ homeostasis is required for cercosporin biosynthesis in Cercospora nicotianae. The addition of excess Ca 2؉ to the medium slightly increased fungal growth but resulted in a reduction in cercosporin production. The addition of Ca

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“…Likewise, neomycin interferes with internal Ca 2+ release through inhibiting phospholipase C activity, binding to phosphoinositides and inhibiting PIP 2 synthesis (Schacht, 1976;Gabev et al, 1989). In addition, neomycin affects inositol phospholipid metabolism by suppressing phosphoinositide kinase and inhibits the activity of phosphatidylcholine-phospholipase D (Liscovitch et al, 1991;Wang et al, 1996).…”

Section: Atpase-driven Hmentioning

confidence: 99%

Calcineurin phosphatase and phospholipase C are required for developmental and pathological functions in the citrus fungal pathogen Alternaria alternata

Tsai

Chung

2014

Microbiology

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Excessive Ca2+ or compounds interfering with phosphoinositide cycling have been found to inhibit the growth of the tangerine pathotype of Alternaria alternata, suggesting a crucial role of Ca 2+ homeostasis in this pathotype. The roles of PLC1, a phospholipase C-coding gene and CAL1, a calcineurin phosphatase-coding gene were investigated. Targeted gene disruption showed that both PLC1 and CAL1 were required for vegetative growth, conidial formation and pathogenesis in citrus. Fungal strains lacking PLC1 or CAL1 exhibited extremely slow growth and induced small lesions on calamondin leaves. Dplc1 mutants produced fewer conidia, which germinated at slower rates than wild-type. Dcal1 mutants produced abnormal hyphae and failed to produce any mature conidia, but instead produced highly melanized bulbous hyphae with distinct septae. Fluorescence microscopy using Fluo-3 dye as a Ca 2+ indicator revealed that the Dplc1 mutant hyphae emitted stronger cytosolic fluorescence, and the Dcal1 mutant hyphae emitted less cytosolic fluorescence, than those of wild-type. Infection assessed on detached calamondin leaves revealed that application of CaCl 2 or neomycin 24 h prior to inoculation provided protection against Alt. alternata. These data indicate that a dynamic equilibrium of cellular Ca 2+ is critical for developmental and pathological processes of Alt. alternata.

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Inhibition of neural phospholipase D activity by aminoglycoside antibiotics

Cited by 54 publications

References 11 publications

Evidence for a Novel K⁺Channel Modulated by α_1A-Adrenoceptors in Cardiac Myocytes

Evidence for a Novel K⁺Channel Modulated by α_1A-Adrenoceptors in Cardiac Myocytes

Involvement of Calcium/Calmodulin Signaling in Cercosporin Toxin Biosynthesis byCercosporanicotianae

Calcineurin phosphatase and phospholipase C are required for developmental and pathological functions in the citrus fungal pathogen Alternaria alternata

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Inhibition of neural phospholipase D activity by aminoglycoside antibiotics

Cited by 54 publications

References 11 publications

Evidence for a Novel K+Channel Modulated by α1A-Adrenoceptors in Cardiac Myocytes

Evidence for a Novel K+Channel Modulated by α1A-Adrenoceptors in Cardiac Myocytes

Involvement of Calcium/Calmodulin Signaling in Cercosporin Toxin Biosynthesis byCercosporanicotianae

Calcineurin phosphatase and phospholipase C are required for developmental and pathological functions in the citrus fungal pathogen Alternaria alternata

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Evidence for a Novel K⁺Channel Modulated by α_1A-Adrenoceptors in Cardiac Myocytes

Evidence for a Novel K⁺Channel Modulated by α_1A-Adrenoceptors in Cardiac Myocytes