Novel antimigraineur dotarizine releases Ca2+ from caffeine‐sensitive Ca2+ stores of chromaffin cells

  title={Novel antimigraineur dotarizine releases Ca2+ from caffeine‐sensitive Ca2+ stores of chromaffin cells},
  author={Jes{\'u}s Novalbos and Francisco Abad‐Santos and Pedro Zapater and Javier Alvarez and Mar{\'i}a Teresa Alonso and Mayte Montero and A. G. Garcı́a},
  journal={British Journal of Pharmacology},
The novel antimigraineur, dotarizine (30 μM), increased cytosolic Ca2+ concentration, [Ca2+]c, in fura‐2‐loaded bovine adrenal chromaffin cells. This increase was transient, reached a peak in about 2–5 min (0.53±0.07 μM; n=19) and then declined to basal levels over a further 5 min period. This transient rise of [Ca2+]c was mimicked by 1 μM thapsigargin and by 30 μM cyclopiazonic acid (CPA), but not by 30 μM flunarizine. Both thapsigargin and CPA occluded the effects of dotarizine and vice versa… Expand
Antimigraine dotarizine blocks P/Q Ca2+ channels and exocytosis in a voltage-dependent manner in chromaffin cells.
Blockade was faster and greater when dotarizine was applied on cells that were previously depolarised with Krebs-HEPES deprived of Ca(2+) and containing increasing concentrations of K(+). Expand
Acute reversible SERCA blockade facilitates or blocks exocytosis, respectively in mouse or bovine chromaffin cells
These drastic differences in the regulation of ACh-triggered secretion at 37 °C may help to understand different patterns of theregulation of exocytosis by the circulation of Ca 2+ at a functional ERCa 2+ store. Expand
Albumin prevents mitochondrial depolarization and apoptosis elicited by endoplasmic reticulum calcium depletion of neuroblastoma cells.
It is suggested that inhibition of mitochondrial depolarization might become a target to develop new anti-apoptotic compounds with therapeutic neuroprotective potential in stroke, Alzheimer's disease, and other neurodegenerative diseases. Expand
Chromaffin cells as a model to evaluate mechanisms of cell death and neuroprotective compounds
In this review, it is shown how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action in different neurodegenerative-related models. Expand
Stimulation of Ca2+ signals in neurons by electrically coupled electrolyte-oxide-semiconductor capacitors
Electrolyte-oxide-semiconductor capacitors are used to control Ca²+ signalling in cultured mammalian cells, including neurons, and evidence is provided that EOSC stimulation with voltage waveforms in the microsecond or nanosecond range activates two distinct Ca�+ pathways. Expand


Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic Ca2+.
Both dotarizine and flunarizines provided protection against veratridine-induced cell death and enhanced the cytotoxic effects of veratidine, and no correlation was found between log P and cytotoxicity. Expand
Dotarizine versus flunarizine as calcium antagonists in chromaffin cells
The results suggest that dotarizine behaves as a Ca2+ antagonist in bovine chromaffin cells and exhibits a potency similar to flunarIZine in blocking Ca2- entry, Ca2+, channels, Cai2+ signals and secretion. Expand
Ca2+-induced Ca2+ Release in Chromaffin Cells Seen from inside the ER with Targeted Aequorin
The results indicate that the ER of chromaffin cells behaves mostly as a single homogeneous thapsigargin-sensitive Ca2+ pool that can release Ca2- both via InsP3 receptors or CICR. Expand
Serotonergic effects of dotarizine in coronary artery and in oocytes expressing 5-HT2 receptors.
It is concluded that dotarizine blocks 5-HT2A receptors with a high affinity; the compound is devoid of intracellular effects on any further steps of the transduction pathway (i.e., IP3 receptor). Expand
Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells.
The results support the idea that the filling state of intracellular Ca2-ATPase stores regulates Ca2+ influx in HL-60 cells. Expand
A caffeine-sensitive Ca2+ store modulates K+-evoked secretion in chromaffin cells.
Functional data are compatible with the view that the degree of filling of a caffeine-sensitive intracellular Ca2+ store might regulate the extent of exocytosis, and the depression of secretion by caffeine does not seem to be associated with inhibition of extracellular Ca 2+ entry through Ca2- channels. Expand
Effects of dotarizine on 45Ca2+ movements and contractile responses in vascular smooth muscle.
Results suggest that, in rabbit, dotarizine inhibits Ca 2+ entry through Ca2+ channels, being more selective for the basilar artery, probably by acting on multiple sites to decrease the availability of intracellular free Ca2+, required for activation. Expand
Drug action of thapsigargin on the Ca2+ pump protein of sarcoplasmic reticulum.
Thapsigargin is the most effective inhibitor of the Ca2+ pump protein of intracellular membranes (SR and endoplasmic reticulum) and its primary inhibitory action appears to inactivate the E2 form of the enzyme preferentially. Expand
Transfected Aequorin in the Measurement of Cytosolic Ca2+ Concentration ([Ca2+]c)
Targeted recombinant aequorins represent to date the most specific means of monitoring [Ca2+] in subcellular organelles (Rizzuto, R., Simpson, A. W. M., Brini, M., and Pozzan, T. (1992) Nature 358,Expand
Dynamics of [Ca2+] in the Endoplasmic Reticulum and Cytoplasm of Intact HeLa Cells
It is shown that Ca2+ release is inhibited progressively when [Ca2+]er decreases below a threshold of about 150 μm, even in the absence of Ca2- pumping or [Ca1+]c increase, which is consistent with a regulation of the inositol 1,4,5-trisphosphate-gated channels by [Ca3+]r. Expand