Disease relevance of GALLOPAMIL HYDROCHLORIDE

• Calcium uptake produced by a potassium contracture in isolated frog twitch fibers was 6.7 +/- 0.8 pmol in 0.7 cm of fiber (mean +/- SEM, 21 observations) in the presence of 30 microM D600 [1].
• 4. The rate-dependent acidosis was inhibited by the organic calcium antagonist D600 (20 mumol l-1) which also inhibited twitch tension [2].
• The Ca2+ channel blockers D600 and verapamil reversed the suppressive effects of hypoxia [3].
• Blocking Ca(2+) influx by D600 did not diminish secretagogue-associated toxicity [4].
• The differential inhibitory effects of D600 on antigen-induced mediator release vs the smooth muscle effects of the various agonists may suggest multiple mechanisms of release or sources of mediators in human airway anaphylaxis [5].

High impact information on GALLOPAMIL HYDROCHLORIDE

• Based on this information, we have identified two aspartic acid residues in RAG1 (D600 and D708) that function specifically in catalysis [6].
• Lanthanum and D600, under conditions in which their access to the plasmalemma has been facilitated by pretreating the cells with cutinase, also markedly extend metaphase and in several instances permanently arrest cells [7].
• Charge movement in skeletal muscle fibers paralyzed by the calcium-entry blocker D600 [8].
• We analyzed two conditional RAG-1 mutants that affect residues quite close in the primary sequence to an active site amino acid (D600), and we found that they exhibit severely impaired recombination in the presence of certain cleavage site sequences [9].
• Partial inhibition of Ca2+ current by methoxyverapamil (D600) reveals spatial nonuniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes [10].

Chemical compound and disease context of GALLOPAMIL HYDROCHLORIDE

• 7. P.l.d. caffeine contractures (10-40 mM) were not maintained and they were not modified by Ca-free saline, Cd2+, Co2+, Mn2+ and D600 [11].
• 3. The tonic component of the K contracture is unaffected by D600 or tetracaine, shows a shallow dependence on membrane potential but is absent in Na-free fluid [12].
• In higher concentrations (3 times 10- minus 4 to 10- minus 3 M) it acts as a calcium antagonistic, like D600, and furthermore may interact with calcium moving through myocardial cell membranes to cause a contracture via a mechanism which it shares with theophylline [13].

Biological context of GALLOPAMIL HYDROCHLORIDE

• D600-induced depression of Isi is shown to be greater after a depolarization (action potential or clamp pulse) than before [14].
• The nicotinic receptor antagonist tubocurarine (4 x 10(-7) M) and the Ca2+ channel blocker D600 (10(-5) M) prevent the subsequent rise of Penk mRNA levels after challenge with nicotine, when given within the lag phase (0-6 h), suggesting the need of continuous receptor occupation and Ca2+ entry for induction of gene expression [15].
• Activation of 28Mg efflux by Na+/o follows hyperbolic kinetics, with Mg2+/o reducing the affinity of the system for Na+/o. Lanthanum and D600 reversibly inhibit Mg efflux [16].
• KCl stimulated Ser-133 phosphorylation of cAMP response element-binding protein (CREB) in chromaffin cells, and CREB phosphorylation was blocked by both ascomycin and D600 [17].
• The Ca2+ channel blocker D600 decreased both the cell fusion and the normal rise in cGMP levels [18].

Anatomical context of GALLOPAMIL HYDROCHLORIDE

• Mechanism of calcium channel block by D600 in single smooth muscle cells from rabbit ear artery [19].
• These findings are compatible with the hypothesis that the primary mode of action of D600 is to inhibit Ca2+ entry in the B-cell [20].
• The association of 125I-labelled LDL with HeLa cells was increased in proportion to the concentration of D600, and 125I-labelled LDL was accumulated in lysosomal fractions as assessed by Percoll density gradient analysis [21].
• Although D600 is not now considered a specific blocker, its effect has suggested the involvement of Ca2+ channels in the acrosome reaction [22].
• Veratridine increased 45Ca uptake into the isolated neurohypophysis and the increase could be prevented by addition of tetrodotoxin or D600 to the medium [23].

Associations of GALLOPAMIL HYDROCHLORIDE with other chemical compounds

• The recognition of glucose by the B-cell was also unaffected by D600 as judged by the effect of the sugar upon both 45calcium efflux and net uptake in the isolated islets [20].
• The mechanism by which the phenylalkylamines, verapamil and D600, and related compounds, block inactivating delayed rectifier K+ currents in rat alveolar epithelial cells, was investigated using whole-cell tight-seal recording [24].
• Redistribution of PKC in response to Buserelin is inhibited by the calcium ion channel antagonist methoxyverapamil (D600), suggesting that redistribution of PKC activity, like GnRH-stimulated gonadotropin release, requires the influx of extracellular calcium [25].
• LH synthesis and release were measured after a 4-h treatment of cells with gallopamil hydrochloride (D600; 1 and 100 microM), a Ca2+ channel blocker, or pimozide (0.5 and 5.0 microM), a calmodulin inhibitor, with or without 1 nM GnRH [26].
• The P/Q-type Ca(2+) channel blocker omega-agatoxin TK (500 nM) and the L-type Ca(2+) channel blocker nifedipine (20 microM) had no effect on the Ca(2+) transient, whereas the L-type Ca(2+) channel blocker methoxyverapamil (D600, 0.5-1 mM) irreversibly reduced the Ca(2+) transient by 37% in axons and by 42% in dendrites [27].

Gene context of GALLOPAMIL HYDROCHLORIDE

• Although treatment with either 1 mM 8Br-cAMP or 1 mM 8Br-GMP failed to increase mAChR number, treatment with either the inorganic Ca2+ channel blocker Co2+ (1 mM) or the organic Ca2+ channel antagonist D600 (10-100 microM) produced 40-80% increases in mAChR number [28].
• The time course and efficacy of LH release in response to GnRH and to MTX are similar; both secretagogues require extracellular Ca2+ and are inhibited by the selective Ca2+ ion channel antagonist methoxyverapamil (D600) [29].
• Treatment of cells with D600 partially blocked CRF-stimulated elevation of POMC mRNA and forskolin-stimulated elevation of PRL mRNA [30].
• An oxytocin antagonist (1 mumol/l solution) significantly reduced basal oxytocin release and blocked the stimulatory effect normally induced by exogenous oxytocin, as did gallopamil hydrochloride (D600, 10 mumol/l solution), a Ca2+ channel blocker, or incubation in a Ca2+-free medium [31].
• This increase in ProEnk A and PNMT mRNA levels was however less affected by D600 [32].

Analytical, diagnostic and therapeutic context of GALLOPAMIL HYDROCHLORIDE

• This effect was not dependent on the presence of D600 (methoxyverapamil) or continuous coronary perfusion [33].
• This study investigated the action of the calcium antagonist D600 on calcium channel currents recorded in high barium solution from single, enzymatically isolated smooth muscle cells from the rabbit ear artery using the whole cell configuration of the patch-clamp technique [19].
• First, in static cultures we used a specific Ca+2 ion channel blocker, methoxyverapamil (D600), to block entry of extracellular Ca+2 into pituitary cell cultures to determine if brief elevation of intracellular Ca+2 (whether derived from external or internal sources) could support continued gonadotropin release [34].
• D890, a derivative of the Ca2+ channel antagonist D600, was intracellularly applied from conventional microelectrodes into pyramidal neurons of neocortical slices [35].
• Methoxyverapamil (D600) in zero Ca2+o did not affect HV in lamprey DA, nor did it prevent further constriction when Ca2+o was restored during hypoxia in hagfish DA [36].

References