Differential effects of maitotoxin on calcium entry and ciliary beating in the rabbit ciliated tracheal epithelium

Venant, Annick; Dazy, Anne-Catherine; Diogène, Jorge; Marano, Francelyne

doi:10.1016/0248-4900(96)85281-6

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…But neither calmodulin inhibitors nor phosphatase inhibitors changed the kinetic relationship between [Ca 2+ ] i and CBF. Okadaic acid has previously failed to inhibit a CBF increase upon Ca 2+ entry into rabbit airway epithelial cells (Venant et al 1995). Despite their utilization in unicellular organisms (e.g.…”

Section: Discussionmentioning

confidence: 99%

Mode of Ca²⁺ action on ciliary beat frequency in single ovine airway epithelial cells

Salathé

Bookman

1999

The Journal of Physiology

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We analysed the kinetics of coupling between cytoplasmic calcium ([Ca2+]i) and ciliary beat frequency (CBF) using simultaneous single cilium recording and single cell [Ca2+]i measurements from cultured ovine tracheal epithelial cells. CBF and [Ca2+]i (indicated by fura‐2) were measured at rest and in response to activation of the G‐protein coupled M3 muscarinic receptor by 10 μM acetylcholine (ACh). Fourier transform analysis of 3 s data segments of light intensity from phase‐contrast microscopy showed no significant delay between changes in [Ca2+]i and CBF during a 2 min exposure to ACh and subsequent washout. CBF time resolution was improved by computing instantaneous beat frequency. This revealed that CBF lagged the rapid increase in [Ca2+]i in response to ACh with a delay of less than 1 beat cycle (143 ms at 7 Hz). When CBF was estimated by an improved Fourier method, this delay was observed to be 70 ± 30 ms (mean ± s.e.m.; n= 20 cilia). During the slower return to baseline, a lag of 8 ± 3.2 s was observed, indicative of hysteresis. While calmodulin inhibitors (calmidazolium and W‐7; each n= 5) decreased baseline CBF by an average of 1.1 ± 0.1 Hz, they did not alter the kinetic relationship between [Ca2+]i and CBF. Similarly, phosphatase inhibitors (okadaic acid and cyclosporin A; each n= 5), changed neither baseline CBF nor the kinetic coupling between [Ca2+]i and CBF. These data suggest that the timing of Ca2+ action on CBF in ovine airway epithelial cells, is unlikely to be determined by phosphorylation reactions involving calmodulin or kinase/phosphatase reactions. A simple model for Ca2+ stimulation of CBF is presented. Fits of the model to the data suggest four or more Ca2+ ions bind cooperatively to speed up CBF.

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Section: Discussionmentioning

confidence: 99%

Mode of Ca²⁺ action on ciliary beat frequency in single ovine airway epithelial cells

Salathé

Bookman

1999

The Journal of Physiology

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“…Maitotoxins may stimulate phospholipid breakdown in the cell membrane due to activation of phospholipase C (Venant et al, 1995). Necrotic cell death is partially mediated by calpain (neutral cytosolic cysteine protease present in central nervous system) activation (Zhao et al, 1999 (Daly et al, 1995) Microcystins (e.g.…”

Section: Clostridium Perfringensmentioning

confidence: 99%

Therapy and prophylaxis of inhaled biological toxins

Paddle¹

2003

J of Applied Toxicology

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This review highlights the current lack of therapeutic and prophylactic treatments for use against inhaled biological toxins, especially those considered as potential biological warfare (BW) or terrorist threats. Although vaccine development remains a priority, the use of rapidly deployable adjunctive therapeutic or prophylactic drugs could be life-saving in severe cases of intoxication or where vaccination has not been possible or immunity not established. The current lack of such drugs is due to many factors. Thus, methods involving molecular modelling are limited by the extent to which the cellular receptor sites and mode of action and structure of a toxin need to be known. There is also our general lack of knowledge of what effect individual toxins will have when inhaled into the lungs - whether and to what extent the action will be cell specific and cytotoxic or rather an acute inflammatory response requiring the use of immunomodulators. Possible sources of specific high-affinity toxin antagonists being investigated include monoclonal antibodies, selected oligonucleotides (aptamers) and derivatized dendritic polymers (dendrimers). The initial selection of suitable agents of these kinds can be made using cytotoxicity assays involving cultured normal human lung cells and a range of suitable indicators. The possibility that a mixture of selected antibody, aptamer or dendrimer-based materials for one or more toxins could be delivered simultaneously as injections or as inhaled aerosol sprays should be investigated.

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“…MTX activation of Phospholipase C (PLC) did not appear to involve Gi or Go, because the response to the toxin was insensitive to pertussis toxin (Gusovsky, Yasumoto, and Daly 1989). Venant et al (1994) also reported that MTX induces calcium uptake in primary cultures of rabbit epithelial cells, and that this activation may not be linked to a trimeric G-protein. Instead, this group proposed that the action of the toxin might result from activation of another type of PLC such as PLC-°, whose activation is dependent on phosphorylation by tyrosine kinase.…”

Section: Figurementioning

confidence: 99%

Effect of Maitotoxin on Guanine Nucleotide Interaction With G-Protein α Subunits

Khan

Tall²,

Rebecchi³

et al. 2001

International Journal of Toxicology

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Maitotoxin is a potent water-soluble polyether toxin produced by the marine dinofiagellate Gambierdiscus toxicus. Although associated with increased calcium uptake, mobilization of internal calcium stores, and enhanced phosphoinositide metabolism, the primary molecular mechanism underlying its actions remains unclear. In this study, we evaluated the effects of maitotoxin (MTX) on the interaction of guanine nucleotides with G-protein alpha subunits. Equilibrium binding of the nonhydrolyzable GTP analog, GTPgammaS, to alpha subunits (Go, Gs, Gi1, Gi2, and Gi3) was decreased in the presence of MTX. Furthermore, reconstitution of Galpha with Gbetagamma dimer showed a reversal of the inhibition elicited by MTX. GDP/GTP exchange rate for Galpha subunits was significantly inhibited in the presence of MTX. MTX had no effect on the rate of GDP or GTP dissociation from alpha subunits. Also, the mastoparan-induced component of nucleotide exchange is not effected by MTX. These results suggest that MTX acts on Galpha subunits to modulate their interaction with guanine nucleotides, perhaps by stabilizing an empty state of the alpha subunit. Accordingly, MTX may disrupt the normal signal transduction pathways by inhibiting GTP binding to Galpha subunits and interfering with the GDP/GTP exchange.

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Differential effects of maitotoxin on calcium entry and ciliary beating in the rabbit ciliated tracheal epithelium

Cited by 6 publications

References 26 publications

Mode of Ca²⁺ action on ciliary beat frequency in single ovine airway epithelial cells

Mode of Ca²⁺ action on ciliary beat frequency in single ovine airway epithelial cells

Therapy and prophylaxis of inhaled biological toxins

Effect of Maitotoxin on Guanine Nucleotide Interaction With G-Protein α Subunits

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Differential effects of maitotoxin on calcium entry and ciliary beating in the rabbit ciliated tracheal epithelium

Cited by 6 publications

References 26 publications

Mode of Ca2+ action on ciliary beat frequency in single ovine airway epithelial cells

Mode of Ca2+ action on ciliary beat frequency in single ovine airway epithelial cells

Therapy and prophylaxis of inhaled biological toxins

Effect of Maitotoxin on Guanine Nucleotide Interaction With G-Protein α Subunits

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Mode of Ca²⁺ action on ciliary beat frequency in single ovine airway epithelial cells

Mode of Ca²⁺ action on ciliary beat frequency in single ovine airway epithelial cells