Effect of dimephosphone on the dynamics of intracellular calcium

2001 ◽  
Vol 82 (2) ◽  
pp. 132-133
Author(s):  
R. A. Giniatullin ◽  
R. R. Giniatullina ◽  
E. M. Sokolova ◽  
R. S. Garaev ◽  
A. O. Vizel
Keyword(s):  
Intracellular Calcium ◽  
Mechanism Of Action ◽  
Calcium Antagonists ◽  
Ionized Calcium ◽  
Fluorescent Signal ◽  
Physiological Signal ◽  
Secondary Messenger ◽  
Highly Sensitive ◽  
Modern Methods ◽  
Depth Study

Intracellular ionized calcium ([Ca2 +] i) - ICIC - is a universal secondary messenger. The physiological signal leading to an increase in its level may be the action of hormones, mediators, trophic agents and other factors. A change in its level may underlie the mechanism of action of a number of drugs. However, until now, only calcium antagonists have become known, which inhibit the entry into the cell of extracellular FCCI. At the end of the 80s, modern methods for registering VKIK were proposed using highly sensitive non-toxic intracellular dyes that change the fluorescent signal with an increase in the concentration of ionized calcium in the cell. This opened up new opportunities for in-depth study of the mechanism of the effect of drugs on the dynamics of intracellular calcium.

scholarly journals The effect of intracellular calcium level regulators on the synthesis of pollen tube callose in Oenothera biennis L.

2014 ◽  
Vol 58 (2) ◽  
pp. 199-210 ◽  
Author(s):  
Elżbieta Bednarska
Keyword(s):  
Pollen Tube ◽  
Calcium Channels ◽  
Intracellular Calcium ◽  
Calcium Antagonists ◽  
Calcium Level ◽  
Ruthenium Red ◽  
Tube Growth ◽  
Oenothera Biennis ◽  
A 23187 ◽  
Intracellular Calcium Level

It is shown that callose synthesis in the <em>Oenothera biennis </em>pollen tube is regulated by the endogenous Ca<sup>2+</sup> level. Calcium antagonists reduced the amount of callose in the wall above the tip of the pollen tube (Verapamil - calcium channels blocker) and at the tube tip after stopping tube growth (La<sup>3+</sup> - a Ca<sup>2+</sup> substitute). Ruthenium red and ionophore A 23187, which raise the Ca 21 level in the cytoplasm, induced callose synthesis at the tip of pollen tube.

The release of slow-reacting substance of anaphylaxis from guinea pig lung: effects of calcium antagonists

1985 ◽  
Vol 63 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Melissa A. Damiano ◽  
Edward J. Barbieri
Keyword(s):  
Guinea Pig ◽  
Intracellular Calcium ◽  
Lung Tissue ◽  
Calcium Antagonists ◽  
Lung Parenchyma ◽  
Free Medium ◽  
Bicarbonate Buffer ◽  
Normal Medium ◽  
Voltage Dependent ◽  
High Concentrations

The effects of three calcium antagonists, verapamil, lanthanum, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) were studied on the release of slow-reacting substance of anaphylaxis (SRS-A) from ovalbumin-sensitized chopped guinea pig lung parenchyma in calcium-containing and calcium-free media. The SRS-A levels (mean ± SEM) obtained from tissues incubated in normal and calcium-free Krebs–bicarbonate buffer were 51 ± 8 (N = 19) and 21 ± 4 (N = 14) U/mL, respectively. TMB-8 (0.1–10 μM) a reported intracellular calcium antagonist, reduced antigen-stimulated SRS-A release from lung tissue incubated in calcium-containing, but not calcium-free, medium; A23187-induced SRS-A release from normal guinea pig lung was not significantly altered by TMB-8 at concentrations up to 10 μM. Verapamil and lanthanum consistently reduced SRS-A release only at high concentrations (100 μM and 1 mM, respectively). The quantities of SRS-A released from lung tissue incubated in the presence of verapamil in normal medium were similar to those obtained in calcium-free medium. Tissues incubated in the presence of potassium chloride (60 and 100 mM) did not release significant quantities of SRS-A, and release which did occur was not blocked by verapamil, suggesting that antigen-induced SRS-A release is not dependent on membrane depolarization and that verapamil was not exerting inhibition via blockade of voltage-dependent calcium channels. These data suggest that although intracellular calcium is important for the regulation of SRS-A secretion from guinea pig lung tissue, extracellular calcium is necessary for optimal release of SRS-A.

ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis

Blood ◽  
2004 ◽  
Vol 103 (1) ◽  
pp. 194-207 ◽  
Author(s):  
Enrico Garattini ◽  
Edoardo Parrella ◽  
Luisa Diomede ◽  
Maurizio Gianni' ◽  
Yesim Kalac ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Intracellular Calcium ◽  
Mechanism Of Action ◽  
Severe Combined Immunodeficiency ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Acetoxymethyl Ester ◽  
Calcium Blockers ◽  
Orally Active

Abstract Retinoid-related molecules (RRMs) are derivatives of retinoic acid and promising antileukemic agents with a mechanism of action different from that of other common chemotherapeutics. Here, we describe a novel chemical series designed against the RRM prototype, CD437. This includes molecules with apoptotic effects in acute promyelocytic leukemia and other myelogenous leukemia cell lines, as well as ST2065, an RRM with antagonistic properties. The most interesting apoptotic agent is ST1926, a compound more powerful than CD437 in vitro and orally active in vivo on severe combined immunodeficiency (SCID) mice that received transplants of NB4 cells. ST1926 has the same mechanism of action of CD437, as indicated by the ability to trans-activate retinoic acid receptor γ, to induce the phosphorylation of p38 and JNK, and to down-regulate the expression of many genes negatively modulated by CD437. ST1926 causes an immediate increase in the cytosolic levels of calcium that are directly related to the apoptotic potential of the RRMs considered. The intracellular calcium elevation is predominantly the result of an inhibition of the mitochondrial calcium uptake. The phenomenon is blocked by the ST2065 antagonist, the intracellular calcium chelator BAPTA (1,2 bis (2-aminophenoxy) ethane-N, N, N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester), and by high concentrations of calcium blockers of the dihydropyridine type, compounds that suppress ST1926-induced apoptosis.

Phase I/II trial of nemorubicin hydrochloride in combination with cisplatin is supported by new preclinical evidences of its mechanism of action

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14116-14116 ◽  
Author(s):  
M. A. Pacciarini ◽  
C. Geroni ◽  
M. A. Sabatino ◽  
M. Ciomei ◽  
O. Valota ◽  
...  
Keyword(s):  
Phase I ◽  
Mechanism Of Action ◽  
Topoisomerase I ◽  
Excision Repair ◽  
Alkylating Agents ◽  
Liver Transaminase ◽  
Highly Sensitive ◽  
Nucleotide Excision ◽  
Combination Studies ◽  
Phase I And Ii

14116 Background: Nemorubicin hydrochloride (nemorubicin) is a non-conventional anthracycline in Phase II evaluation in hepatocellular carcinoma (HCC). Its mechanism of action is not fully elucidated. Although structurally related to doxorubicin, nemorubicin is a topoisomerase I inhibitor, overcomes anthracyclines resistance, is minimally cardiotoxic and is biotransformed by hepatic CYP3A4 into hundred times more cytotoxic metabolite. Phase I and II trials were conducted in Europe and China to test nemorubicin by hepatic intra-arterial (IHA) infusion in HCC patients (pts). The drug was well tolerated up to 600 mcg/m2 q4–6w; DLT was transient liver transaminase elevations. Overall, 57 HCC pts were evaluable for efficacy, with 11/57 confirmed liver CR/PRs (RR = 19.3%; 95% ci 10–31.9%) lasting 1–54+ months. Stable disease ≥ 3 months was observed in 17/57 (29.8%) pts, most with AJCC Stage III, IIIA and IVA. These data supported new trials of nemorubicin in HCC. Methods: To further characterize the mechanism of action of the drug, we generated cells (L1210) resistant to nemorubicin. Since resistant cells were more sensitive than the parental ones to UV irradiation, we reasoned that the nucleotide excision repair (NER) system might be involved in mediating the activity of nemorubicin. To test this hypothesis we used isogenic CHO cells proficient or deficient in excision repair cross-complementing (ERCC) genes, namely ERCC1 and ERCC6 genes. Results: In contrast with what is observed for most DNA damaging drugs that show resistance in the presence of high NER activity, nemorubicin is more cytotoxic in NER proficient than in deficient cells. This suggests that NER pathway plays a role in the cytotoxic effect of nemorubicin. Also, cells resistant to nemorubicin are NER-deficient and are highly sensitive to platinum derivatives and alkylating agents and synergism was found combining cisplatin with nemorubicin. Conclusions: Nemorubicin has a peculiar mechanism of action through the NER system providing the rationale for clinical combination studies with platinum derivatives. A Phase I/II trial of nemorubicin with cisplatin in HCC patients started in Italy at the end of 2005. No significant financial relationships to disclose.

The effects of HA compound calcium antagonists on delayed cerebral vasospasm in dogs

1986 ◽  
Vol 65 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Masakazu Takayasu ◽  
Yoshio Suzuki ◽  
Masato Shibuya ◽  
Toshio Asano ◽  
Masahiko Kanamori ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracellular Calcium ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Calcium Antagonists ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Delayed Cerebral Vasospasm ◽  
Arterial Blood

✓ The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquino-linesulfonamide) and HA1077(l-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 × 10−6 M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10−5 M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10−5 M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a “two-hemorrhage” canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% ± 2% (mean ± standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.

The influence of dihydropyridines calcium antagonists on 5-HT-induced intracellular calcium signal

2007 ◽  
Vol 50 (4) ◽  
pp. 562-567
Author(s):  
ShuMin Wang ◽  
HuaShi Guan ◽  
Yi Fang ◽  
Ping Ma ◽  
JianZi Sun ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Antagonists ◽  
Calcium Signal

scholarly journals Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists

1995 ◽  
Vol 30 (2) ◽  
pp. 212-221 ◽  
Author(s):  
C. E. Zaugg ◽  
S. Kojima ◽  
S. T. Wu ◽  
J. Wikman-Coffelt ◽  
W. W. Parmley ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Antagonists ◽  
Calcium Transients ◽  
Rat Hearts ◽  
Force Relationship
Sign in / Sign up

Export Citation Format

Share Document