Action of papaverine and ionophore A23187 on neurulation

Moran, Denis; Rice, Robert W.

doi:10.1038/261497a0

Cited by 66 publications

(22 citation statements)

References 16 publications

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“…These results agree with those of Moran and Rice (14), who showed that the papaverine-induced inhibition of neurulation was counteracted by A23187. These results suggest that papaverine and verapamil inhibit or block specific gates for cellular Ca2+ entry that are located in the plasma membranes.…”

Section: Discussionsupporting

confidence: 93%

Optic cup formation: a calcium-regulated process.

Brady¹,

Hilfer²

1982

Proc. Natl. Acad. Sci. U.S.A.

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Invagination of the optic vesicle to form the optic cup is an important event in the formation of the eye in the early embryo. To obtain support for earlier conclusions that a contractile process is involved, calcium dependency ofoptic cup formation was tested. Heads were excised from chicken embryos at the optic vesicle stage of development (stage 13) and incubated in nutrient medium containing antagonists or agonists of calcium transport. Invagination was reversibly inhibited by the Ca2+ antagonists verapamil and papaverine. It was initiated in a precocious fashion by the Ca2+ ionophore A23187 but only in the presence of external Ca2+. Neither caffeine, theophylline, nor A23187 (in the absence of external Ca2+) were able to initiate precocious optic cup formation. Trifluoperazine and chlorpromazine reversibly inhibited optic cup formation while chlorpromazine sulfoxide had no effect at the concentrations used. Reagents. The calcium ionophore A23187 was purchased from Calbiochem-Behring and was dissolved in dimethyl sulfoxide. Theophylline, papaverine, and caffeine were purchased from Sigma. Verapamil was supplied by Knoll Pharmaceutical (Whippany, NJ). Trifluoperazine (TFP), [3H]TFP (67 ,uCi/mg; 1 Ci = 3.7 X 10O' becquerels), chlorpromazine (CPZ), and chlorpromazine sulfoxide (CPZ-S02) were the gifts of Smith Kline & French.Antisera. Sheep anticalmodulin (rat testis) was the gift of John Dedman (University of Texas Medical School). Fluorescein-conjugated rabbit anti-sheep IgG was purchased from GIBCO.Culture Experiments. All cultures were incubated at 37°C in medium 199 (GIBCO) in humid 5% C02/95% air. The inhibitory effects of various drugs were studied in an overnight culture system. The heads of stage 12 to 13 chicken embryos were excised, placed in medium containing a variety of concentrations of calcium antagonists or phenothiazines, and then incubated for 18 hr. The phenothiazines and papaverine were dissolved in water and diluted to the appropriate concentrations with medium. Verapamil was dissolved in 95% ethanol. Control heads were placed in medium containing no drug and incubated in parallel with each group of experimental heads. After 18 hr, experimental heads were examined by light microscopy and compared with controls for optic cup formation. Photographs were taken through a Wild M5 (Wild-Heerbrugg, Farmingdale, NY) dissecting microscope. Precocious optic cup formation in response to calcium agonists was assessed in a short-term (30-min) culture system.[3H]TFP Binding Studies. Heads of stage 13 chicken embryos were excised with extreme care to ensure equal size. They were incubated at 37°C in the presence of various concentrations of [3H]TFP (67 ,Ci/mg) for various periods of time as stated in the figures. After incubation, each head was individually transferred through three successive wash vials containing 10 ml of ice-cold medium. The medium used for washing was always the same as that used in the initial incubation except that it contained no drug. Each head was kept in each wash vi...

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Section: Discussionsupporting

confidence: 93%

Optic cup formation: a calcium-regulated process.

Brady¹,

Hilfer²

1982

Proc. Natl. Acad. Sci. U.S.A.

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“…Ca 2+ binds to and activates its target proteins that control diverse biological phenomena, such as cell proliferation, muscle contraction, gene expression and cellular movement (Clapham, 2007;Markova and Lenne, 2012). Inhibiting Ca 2+ influx causes NTC to fail (Lee and Nagele, 1986;Smedley and Stanisstreet, 1986), while inducing an increase in intracellular Ca 2+ promotes folding morphogenesis of the NP (Ferreira and Hilfer, 1993;Moran and Rice, 1976). Since these effects at the tissue level are accompanied by changes in cell shape (Ferreira and Hilfer, 1993), intracellular Ca 2+ signaling has been proposed to regulate AC, although the detailed molecular mechanism is unclear.…”

Section: +mentioning

confidence: 99%

Distinct intracellular Ca2+ dynamics regulate apical constriction and differentially contribute to neural tube closure

et al. 2017

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Early in the development of the central nervous system, progenitor cells undergo a shape change, called apical constriction, that triggers the neural plate to form a tubular structure. How apical constriction in the neural plate is controlled and how it contributes to tissue morphogenesis are not fully understood. In this study, we show that intracellular calcium ions (Ca 2+ ) are required for Xenopus neural tube formation and that there are two types of Ca 2+ -concentration changes, a single-cell and a multicellular wave-like fluctuation, in the developing neural plate. Quantitative imaging analyses revealed that transient increases in Ca 2+ concentration induced cortical F-actin remodeling, apical constriction and accelerations of the closing movement of the neural plate. We also show that extracellular ATP and N-cadherin (cdh2) participate in the Ca 2+ -induced apical constriction. Furthermore, our mathematical model suggests that the effect of Ca 2+ fluctuations on tissue morphogenesis is independent of fluctuation frequency and that fluctuations affecting individual cells are more efficient than those at the multicellular level. We propose that distinct Ca 2+ signaling patterns differentially modulate apical constriction for efficient epithelial folding and that this mechanism has a broad range of physiological outcomes.

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“…Even if such material does not actively push up the neural folds, there may be a permissive requirement for a resistance to compression to allow active changes in the shapes of the neuroepithelial cells. It is of interest therefore that papaverine, an inhibitor of calcium movement, has the dual effect of making amphibian embryos less turgid and of preventing neurulation (Moran, & Rice, 1976).…”

Section: Role Of the Deficiencies In The Non-neural Tissue In The Orimentioning

confidence: 99%

Computer modelling of neural tube defects

1991

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Neurulation, the curling of the neuroepithelium to form the neural tube, is an essential component of the development of animal embryos. Defects of neural tube formation, which occur with an overall frequency of one in 500 human births, are the cause of severe and distressing congenital abnormalities. However, despite the fact that there is increasing information from animal experiments about the mechanisms which effect neural tube formation, much less is known about the fundamental causes of neural tube defects (NTD). The use of computer models provides one way of gaining clues about the ways in which neurulation may be compromised. Here we employ one computer model to examine the robustness of different cellular mechanisms which are thought to contribute to neurulation. The model, modified from that of Odell et al (Odell, G.M., Oster, G., Alberch, P. and Burnside, B., (1981)) mimics neurulation by laterally propagating a wave of apical contraction along an active zone within a ring of cells. We link the results to experimental evidence gained from studies of embryos in which neurulation has been perturbed. The results indicate that alteration of one of the properties of non-neural tissue can delay or inhibit neurulation, supporting the idea, gained from observation of embryos bearing genes which predispose to NTD, that the tissue underlying the neuroepithelium may contribute to the elevation of the neural folds. The results also show that reduction of the contractile properties of a small proportion of the neuroepithelial cell population may have a profound effect on overall tissue profiling. The results suggest that the elevation of the neural folds, and hence successful neurulation, may be vulnerable to relatively minor deficiencies in cell properties.

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Action of papaverine and ionophore A23187 on neurulation

Cited by 66 publications

References 16 publications

Optic cup formation: a calcium-regulated process.

Optic cup formation: a calcium-regulated process.

Distinct intracellular Ca2+ dynamics regulate apical constriction and differentially contribute to neural tube closure

Computer modelling of neural tube defects

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