Phospholipid-sensitive calcium-dependent protein kinase: Inhibition by antipsychotic drugs

Schatzman, Randall C.; Wise, Bradley C.; Kuo, J.F.

doi:10.1016/0006-291x(81)91166-9

Cited by 240 publications

(69 citation statements)

References 11 publications

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“…The concentrations for half-maximal inhibition were about 0.45 and 1 mM for dibucaine and tetracaine, respectively. Although the concentrations were significantly greater than those needed for phenothiazine inhibition, they reflected the concentrations required for anaesthetic effects on other membrane processes (26). In fact, a linear relationship existed between the log of the octanol-water partitioning coefficient for dibucaine, tetracaine, and chlorpromazine and the concentration needed for half-maximal inhibition of Ca2+ uptake (data not shown).…”

Section: Resultsmentioning

confidence: 93%

“…This binding was based on a hydrophobic interaction. Because of their hydrophobicity, phenothiazines affected processes other than those mediated by calmodulin (24,26). Since the phenothiazines inhibited Ca2" uptake but authentic calmodulin did not affect Ca2+ uptake, the mode of action of these drugs might be related to a more general hydrophobic interaction with the membrane rather than a specific interaction with a calmodulin-regulated process.…”

Section: Resultsmentioning

confidence: 99%

“…Since the phenothiazines inhibited Ca2" uptake but authentic calmodulin did not affect Ca2+ uptake, the mode of action of these drugs might be related to a more general hydrophobic interaction with the membrane rather than a specific interaction with a calmodulin-regulated process. Local anaesthetics also interact hydrophobically with membranes (26).…”

Section: Resultsmentioning

confidence: 99%

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Characterization of Ca²⁺ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Buckhout

1984

Plant Physiol.

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The characteristics of Ca2" transport into endoplasmic reticulum vesicles isolated from roots of Lepidium sativum L. cv Krause have been investigated. The concentration of free Ca2 and ATP needed for halfmaximal activity were 2.5 and 73 micromolar, respectively, and the enzyme obeyed Michaelis-Menten-like kinetics. The pH maximum occurred at 7.5 and the activity was greatly reduced at either pH 7.0 or 8.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Characterization of Ca²⁺ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Buckhout

1984

Plant Physiol.

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“…From the results in this paper, an extension of this hypothesis is suggested to include a Ca2+ involvement in the ion flux. Whether the two classes of inhibitor are inhibiting betacyanin synthesis by reacting with phospholipid (30) or with calmodulin (34) would not affect this general conclusion. Caution would still need to be exercised, however, to accommodate the possibility of a structurally nonspecific hydrophobic binding to membranes by the drugs with subsequent inhibition of some membrane-bound cytokinin effect, not necessarily involving Ca2+.…”

Section: Discussionmentioning

confidence: 93%

Inhibition of Cytokinin-Regulated Responses by Calmodulin-Binding Compounds

Elliott¹

1983

Plant Physiol.

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Two classes of compous which bind to calnodulin in a calciumdependent manner (neuroleptic drugs and local anaesthetics) were used to investigate the possible involvement of a calcium-dependent regulator protein in the action of the plant hormones cytokinins.The cytokinin-induced synthesis of betacyanin in Amarandus tricolr seedlings was used as one test system. The calmodulin antagonists inhibited betacyanin synthesis with the following order of potency: fluphenazine > trifluoperazine = pimozide > chlorpromazine > dibucaine > penfluridol > haloperidol > tetracaine, over a concentration range (ICs,) KV. This conclusion is supported by inhibitory effects of uncouplers used for destroying proton fluxes and of inhibitors of membrane ATPases (5).Previous work on the Amaranthus system has, in addition, given evidence of Ca2" involvement in betacyanin accumulation (see Discussion). Hence, in view of the widespread involvement of calmodulin in many Ca2"-regulated events (see references in Ref.#9), the present study was undertaken to see if certain drugs which inhibit calmodulin-dependent processes have any effect on the cytokinin-regulation of betacyanin synthesis. Preliminary experiments on the use of trifluoperazine m this system have been reported (9). The second cytokinin-regulated response (control of cell division in cell cultures) was included in this study to explore the generality of the drug effects on cytokinin action. MATERIALS AND METHODSChemicals. Benzyladenine, dibucaine, chlorpromazine, tetracaine, and L-tyrosine were from Sigma. Generous gifts of chemicals were received from the following companies: E.R. Squibb and Sons (fluphenazine dihydrochloride), Searle Laboratories (haloperidol), Janssen Pharmaceutica Pty. Ltd. (pimozide and penfluridol), Smith, Kline, and French Laboratories (trifluoperazine).Standard Assay Conditions for Betacyanin Accunulation. Methods have been described elsewhere (7) for the germination of seeds ofAmaranthus tricolor and the pretreatment ofhalf-seedlings (ie. cotyledons plus the top 5 mm of the hypocotyl). Aging of half-seedlings in water (1.5 h at 40°C followed by 1.5 h at 25°C) was found to maximize subsequent cytokinin-induction. The basic induction-medium was 5 mM L-tyrosine (betacyanin precursor) in 10 mm K2HPO4-NaH2PO4 (pH 6.8) ± 0.5 ,UM BA (synthetic cytokinin), and the incubation was at 25°C for 24 h in the dark. Betacyanin was extracted in 3.33 mm acetic acid and measured at 537 nm (7).Soybean Callus Assay. The procedure of Miller (24) was used for the growth of soybean callus material and the assay of cytokinin-dependent growth. Cultures were maintained on standard medium with the addition of 0.5 pM BA and 30 ,UM IAA. RESULTSAssays of betacyanin accumulation in Amaranthus half-seedlings in the absence and presence of BA (0.5 ,UM) are shown in Table I

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“…TFP antagonizes the action of phospholipid-sensitive Ca2+-dependent protein kinase (PKC) (Schatzman, Wise & Kuo, 1981) in addition to calmodulin-dependent enzymes. Therefore, it remained possible that the effect of TFP on CBF might be due to PKC inhibition.…”

Section: Effect Of Calcium Ionophore On Intracellular Free Calciummentioning

confidence: 99%

Calcium regulation of ciliary beat frequency in human respiratory epithelium in vitro.

Benedetto

Magnus

Gray

et al. 1991

The Journal of Physiology

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SUMMARY1. The changes in ciliary beat frequency (CBF) of human nasal respiratory epithelial cells were measured in vitro with a photometric technique following exposure to either 4-bromo-calcium ionophore A23187 (4-Br-A23187) or trifluoperazine (TFP), an inhibitor of calmodulin-sensitive calcium-dependent protein kinases. Changes in intracellular free calcium concentrations in response to 4-Br-A23187 were studied using a fluorescent dye (Fura-2).2. Addition of 10' M-4-Br-A23187 caused a time-dependent (P < 001) rise in CBF. The increment in CBF was statistically significant 10 min after challenge (+ 10 %; P < 0 01) and was sustained for at least 1 h, with maximal stimulation after 40 min (+ 18 %; P < 0-01).3. Exposure to 10' M-4-Br-A23187 caused an immediate increase in intracellular free calcium concentration, which preceded the rise in CBF.4. TFP (10' M) caused a reduction of baseline CBF (-10%; P < 001) and prevented the expected rise when the cells were subsequently exposed to 10' M-4-Br-A23187.5. We conclude that: (1) calcium ionophore stimulates the CBF of human respiratory cells; (2) this effect is mediated through a calmodulin-sensitive system, since it is abolished in the presence of TFP; (3) the same pathway appears to control the basal CBF of these cells, since TFP also decreases CBF.

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Phospholipid-sensitive calcium-dependent protein kinase: Inhibition by antipsychotic drugs

Cited by 240 publications

References 11 publications

Characterization of Ca²⁺ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Characterization of Ca²⁺ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Inhibition of Cytokinin-Regulated Responses by Calmodulin-Binding Compounds

Calcium regulation of ciliary beat frequency in human respiratory epithelium in vitro.

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Phospholipid-sensitive calcium-dependent protein kinase: Inhibition by antipsychotic drugs

Cited by 240 publications

References 11 publications

Characterization of Ca2+ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Characterization of Ca2+ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Inhibition of Cytokinin-Regulated Responses by Calmodulin-Binding Compounds

Calcium regulation of ciliary beat frequency in human respiratory epithelium in vitro.

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Product

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Characterization of Ca²⁺ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots

Characterization of Ca²⁺ Transport in Purified Endoplasmic Reticulum Membrane Vesicles from Lepidium sativum L. Roots