Can calmodulin inhibitors be used to probe calmodulin effects?

Landry, Yves; Amellal, M.; Ruckstuhl, M.

doi:10.1016/0006-2952(81)90217-3

Cited by 101 publications

(23 citation statements)

References 8 publications

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“…Cinnarizine caused greater inhibition than did trifluoperazine. The low sensitivity (Landry, Amellal & Ruckstuhl, 1981;Roufogalis, 1981).…”

Section: Calcium-antagonists In Skinned Musclementioning

confidence: 99%

Direct inhibitory effects of some ‘calcium‐antagonists’ and trifluoperazine on the contractile proteins in smooth muscle

Spedding¹

1983

British J Pharmacology

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Taenia preparations from the guinea‐pig caecum were treated with Triton X‐100 and glycerol to disrupt the plasma membrane. Disruption of the sarcolemma was confirmed by electronmicroscopy. The preparations contracted in response to low concentration of Ca2+ (10–40 μM) and the contractions were dependent upon exogenous adenosine triphosphate (ATP). Nifedipine (100 μM), verapamil (100 μM) and diltiazem (100 μM) did not inhibit Ca2+‐induced activation of the contractile proteins. In contrast, fendiline (100 μM), cinnarizine (100 μM), flunarizine (100 μM), pimozide (100 μM) and trifluoperazine (100 μM) significantly inhibited Ca2+‐induced contractions. The effects of cinnarizine (100 μM) were reversible. These findings disclose further differences between calcium‐antagonists and suggest that certain of these agents have an intracellular site of action.

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“…Cinnarizine caused greater inhibition than did trifluoperazine. The low sensitivity (Landry, Amellal & Ruckstuhl, 1981;Roufogalis, 1981).…”

Section: Calcium-antagonists In Skinned Musclementioning

confidence: 99%

Direct inhibitory effects of some ‘calcium‐antagonists’ and trifluoperazine on the contractile proteins in smooth muscle

Spedding¹

1983

British J Pharmacology

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“…However, the usefulness of terbium or other lanthanides as probes of calmodulin has not been shown at the level of intact cells or tissue, whereas changes in the intracellular concentration of calcium ions provide the control for many physiological processes including secretion. The intervention of calmodulin in the release of histamine from rat mast cells has been suggested, in view of the inhibition of release by calmodulin inhibitors (Landry, Amellal & Ruckstuhl, 1980;Douglas & Nemeth, 1982). Foreman, Mongar & Gomperts (1973) showed that ionophore A23187, which selectively increases the permeability of mast cell membrane to calcium, induced histamine release.…”

Section: Introductionmentioning

confidence: 99%

Lanthanides are transported by ionophore A23187 and mimic calcium in the histamine secretion process

Amellal

Landry

1983

British J Pharmacology

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“…The specific IDSOs for inhibition of transformation by the drugs were, in descending order of potency: R24571, 3 pM; TFP, 8 pM; CPMZ, 30 pM; and CPMZSO, greater than 100 pM. These IDSos correspond closely to the reported potencies of these drugs as in vitro inhibitors of calmodulindependent enzyme activation [Gietzen, Wuthrich and Bader, 1981;Landry, Amellal and Ruckstuhl, 1981;Levin and Weiss, 1976;Levin and Weiss, 1977;Weiss and Wallace, 19801 and to those reported for inhibition of other cellular shape changes [Connor, Brady, and Brownstein, 1981;Kao, Sommer and Pizzo, 1981;Nelson, Andrews and Karnovsky, 19831. In all drugs tested, inhibited cells retain their normal petaloid morphology in hypotonic medium.…”

Section: R24571 (0) Tfp (@) Cpmz (O) Cpmzso (A) Error Barsmentioning

confidence: 51%

Calmodulin and caimodulin‐binding proteins in the morphological transformation of sea urchin coelomocytes

Venuti

Edds

1986

Cell Motil. Cytoskeleton

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Sea urchin coelomocytes contain an actin-based cytoskeleton that undergoes major organizational changes as the cells transform from one morphology (petaloid) to another (filopodial). The molecular mechanisms directing and regulating this cytoskeletal reorganization are not well understood; Ca2+ has been implicated, but the specific targets of its action have not been identified. Since the effect of Ca2+ on a variety of cellular processes has been shown to be mediated by the Ca2+-binding protein calmodulin, we investigated the role of this protein in coelomocyte morphological transformation. The calmodulin inhibitory drugs trifluoperazine, chlorpromazine, and calmidazolium were shown to inhibit coelomocyte morphological transformation in response to hypotonic shock in a dosedependent fashion and at concentrations consistent with their reported potencies as anti-calmodulin agents. Calmodulin isolated from coelomocytes using trifluorophenothiazine affinity chromatography co-migrates with bovine brain calmodulin on 15% SDS-polyacrylamide gels and demonstrates a characteristic shift in electrophoretic mobility in the presence of Ca2+. Another diagnostic for calmodulin, Ca2+-dependent activation of exogenous 3'15' cyclic AMP phosphodiesterase, was demonstrated by whole coelomocyte homogenates, heat-treated homogenates, and the affinity purified coelomocyte protein. Localization of calmodulin in coelomocytes by indirect immunofluorescence reveals an association of calmodulin, at least in part, with the actin-based cytoskeleton. Calmodulinbinding polypeptides with estimated relative mobilities of 240,000, 195,000, 170,000, 70,000, 60,000, 30,000, and 20,000 daltons were identified using '251-calmodulin overlay procedures. Ca2+-dependent calmodulin-binding in these preparations was demonstrated for all but the M, 30,000 and 20,000 coelomocyte polypeptides. The majority of the calmodulin-binding proteins identified in whole petaloid coelomocyte preparations are also found in Triton X-100 insoluble cytoskeletal fractions. Immunoblotting with antiserum raised against chicken erythrocyte alpha-spectrin suggests that the 240,000 M, calmodulin-binding polypeptide corresponds to coelomocyte alpha-spectrin. This protein was enriched in isolated coelomocyte filopodia where, we propose, it serves an analogous function to its counterpart in erythrocytes, in linking the actin-cytoskeleton to the plasma membrane. Thus, calmodulin is present in coelomocytes and possibly participates in the morphological transformation of these cells through regulation of cytoskeletal and/or membrane-cytoskeletal interactions.

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Can calmodulin inhibitors be used to probe calmodulin effects?

Cited by 101 publications

References 8 publications

Direct inhibitory effects of some ‘calcium‐antagonists’ and trifluoperazine on the contractile proteins in smooth muscle

Direct inhibitory effects of some ‘calcium‐antagonists’ and trifluoperazine on the contractile proteins in smooth muscle

Lanthanides are transported by ionophore A23187 and mimic calcium in the histamine secretion process

Calmodulin and caimodulin‐binding proteins in the morphological transformation of sea urchin coelomocytes

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