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Results for “Calcium Channels”

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At least 919 records · Page 51Linked to original sources

PubMed1999

Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.

P-type and Q-type calcium channels mediate neurotransmitter release at many synapses in the mammalian nervous system. The alpha 1A calcium channel has been implicated in the etiologies of conditions such as episodic ataxia, epilepsy and familial migraine, and shares several properties with native P- and Q-type channels. However, the exact relationship between alpha 1A and P- and Q-type channels is unknown. Here we report that alternative splicing of the alpha 1A subunit gene results in channels with distinct kinetic, pharmacological and modulatory properties. Overall, the results indicate that alternative splicing of the alpha 1A gene generates P-type and Q-type channels as well as multiple phenotypic variants.

Alternative Splicing↗

PubMed1987

Dihydropyridine-sensitive calcium channels in cardiac and skeletal muscle membranes: studies with antibodies against the alpha subunits.

Polyclonal antibodies (PAC-2) against the purified skeletal muscle calcium channel were prepared and shown to be directed against alpha subunits of this protein by immunoblotting and immunoprecipitation. These polypeptides have an apparent molecular weight of 162,000 without reduction of disulfide bonds. Under conditions where the functional properties of the purified skeletal muscle calcium channel are retained, beta subunits (Mr 50,000) and gamma subunits (Mr 33,000) are coprecipitated, demonstrating specific noncovalent association of these three polypeptides in the purified skeletal muscle channel. PAC-2 immunoprecipitated cardiac calcium channels labeled with [3H]isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5- (methoxycarbonyl)pyridine-3-carboxylate ([3H]PN200-110) at a 3-fold higher concentration than skeletal muscle channels. Preincubation with cardiac calcium channels blocked only 49% of the immunoreactivity of PAC-2 toward skeletal muscle channels, indicating that these two proteins have both homologous and distinct epitopes. The immunoreactive component of the cardiac calcium channel was identified by immunoprecipitation and polyacrylamide gel electrophoresis as a polypeptide with an apparent molecular weight of 170,000 before reduction of disulfide bonds and 141,000 after reduction, in close analogy with the properties of the alpha 2 subunits of the skeletal muscle channel. It is concluded that these two calcium channels have a homologous, but distinct, alpha subunit as a major polypeptide component.

Animals↗

PubMed1998

[Intracellular calcium channels, hormone receptors and intercellular calcium waves].

The hormone-mediated intercellular Ca2+ waves were analyzed in multiplets of rat hepatocytes by video imaging of fura2 fluorescence. These multicellular systems are composed of groups of several cells (doublets to quintuplets) issued from the liver cell plate, a one cell-thick cord of about 20 hepatocytes long between portal and centrolobular veins. When the multiplets were homogeneously bathed with the glycogenolytic agonists vasopressin, noradrenaline, angiotensin II and ATP, they showed highly organized Ca2+ signals. Surprisingly, for a given agonist, the primary rises in intracellular Ca2+ concentration ([Ca2+]i) originated invariably in the same hepatocyte, then was propagated in a sequential manner to the nearest connected cells (cell 2, then 3, cell 4 in a quadruplet, for example). The sequential activation of the cells appeared to be an intrinsic property of multiplets of rat hepatocytes. The same sequence was observed at each train of oscillations occurring between cells. The order of [Ca2+]i responses was modified neither by repeated additions of hormones nor by the hormonal dose. The mechanical disruption of an intermediate cell did not prevent the activation of the next cell. These results suggest that each hepatocyte in the multiplet displays its own sensitivity to the hormone and that a gradient of sensitivity between each cell could be responsible for directing the intercellular Ca2+ wave. To test this hypothesis, we selectively isolated rat hepatocytes from periportal (PP) and perivenous (PV) areas of the liver cell plate. Periportal (PP) and perivenous (PV) rat hepatocyte suspensions were loaded with quin2/AM and hormonal responses were studied in a spectrofluorimeter. Noradrenaline, angiotensin II, and vasopressin-induced [Ca2+]i rises were greater in PV than in PP hepatocytes. In contrast, PP cells were more responsive than PV cells to ATP. The function of the InsP3 receptor (InsP3R) was also studied by measuring the InsP3-mediated 45Ca2+ release from permeabilized PP and PV hepatocytes. In permeabilized PP and PV hepatocytes, internal Ca2+ stores displayed the same loading-kinetics, the responses to InsP3 were similar, and the sizes of InsP3-sensitive compartment were not different. In a further study, we investigated by video microscopy in fura2-loaded multicellular systems of rat hepatocytes, the mechanisms controlling intercellular propagation of the Ca2+ wave and coordination of Ca2+ signals induced by the different hormones. Using focal microperfusion which allows local perfusion of any cell of the multiplet, rapid agonist removal during the Ca2+ response and microinjection, we found that second messengers and [Ca2+]i rises in one hepatocyte cannot trigger Ca2+ responses in connected adjacent cells, suggesting that diffusion across gap junctions, while required for coordination, is not sufficient by itself for the propagation of the intercellular Ca2+ wave. In addition, focal microperfusion and intermediate cell disruption experiments revealed very fine functional differences (hormonal delay, frequency of [Ca2+]i oscillations) between hormone-induced Ca2+ signals, even between two adjacent connected hepatocytes. Recent unpublished results performed in suspensions of PP and PV rat hepatocytes supported the view of a major role played by vasopressin receptors (V1a) in genesis and orientation of the Ca2+ wave. Vasopressin binding sites, V1a mRNAs detected by RNAse Protection Assay, and vasopressin-induced InsP3 production, were more abundant in PV than in PP cells. A gradient of hormone receptors could orientate the propagation of the Ca2+ wave in multicellular systems and in liver cell plate. These results suggest that the intercellular Ca2+ wave in multicellular systems of rat hepatocytes is propagated through mechanisms involving at least three factors. (ABSTRACT TRUNCATED)

Animals↗

PubMed1991

[The effect of calcium channel blockers on experimental hypercholesteremia in rabbits. Biochemical and histochemical study].

Calcium ions act as intracellular messengers in numerous cellular functions and participate also in the development of the atherosclerotic process. Calcium homeostasis could be an important factor in the development of atherosclerosis. One of the drugs which interferes with calcium homeostasis are calcium channel blockers. A number of studies have investigated the possibility whether these drugs may be also useful for prevention of atherosclerosis. However, other investigators have reported that calcium channel blockers did not suppress the atherosclerotic process. In our work we assumed the direct influence of calcium channel blockers on transendothelial transport mechanisms. Therefore we decided to investigate the influence of verapamil, diltiazem and isradipine on the development of experimental atherosclerosis in rabbits. Verapamil administered twice daily, 0.125 mg per kg s. c., reduced the size of atheromatous plaques in the thoracic aorta and the level of total cholesterol and triglycerides in serum. This above effect was not present after administration of diltiazem in doses of 1.0 mg per kg and isradipine 1.25 mg per kg twice daily subcutaneously. Our conclusion is that the anti-atherosclerotic effect of calcium channel blockers is dose-dependent. It is not clear whether this effect takes place in the plasma compartment and/or in the intracellular compartment.

Animals↗

PubMed1996

Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating.

Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitation-contraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode of 70 ms (slow gating); a small number of openings had short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six-state cyclical model is proposed for the DHP-sensitive Ca channel, which pictures the normal pathway of activation of the calcium channel as two voltage-dependent steps in sequence, plus a voltage-independent step which is rate limiting. The model reproduced well the fast and slow gating models of the calcium channel, and the effects of conditioning pulses. It is possible that the voltage-sensitive gating transitions of the DHP receptor, which occur early in the calcium channel activation sequence, could underlie the role of the voltage sensor and yield the rapid excitation-contraction coupling in skeletal muscle, through either electrostatic or allosteric linkage to the ryanodine receptors/calcium release channels.

Animals↗

PubMed1993

Adaptive changes in numbers of calcium channels in drug dependence.

Adrenal-derived cells in culture slowly upregulate numbers of putative calcium channel proteins in response to inhibitory drugs including ethanol, benzodiazepines and morphine. This appears to be an adaptive response to cell inhibition involving second messengers and protein phosphorylation and culminating in alterations in expression of the calcium channel gene (Fig. 1). These increases in calcium channels lead to rebound increases in cell excitability when the depressant drugs are withdrawn (a characteristic feature of chemical dependence on depressant drugs) so that this change in numbers of calcium channels may provide a model for one mechanism of chemical dependence. Similar findings have been reported in the brains of animals made dependent on depressant drugs, and genetic and pharmacological manipulations of dependence and withdrawal further support a role for calcium channels in these phenomena.

Adaptation, Physiological↗

PubMed1996

Identification of binding sites for calcium channel antagonists.

The binding sites of three typical calcium channel antagonists, 1, 4-dihydropyridines, benzothiazepines and phenylalkylamines, were successfully identified within the primary structures of calcium channels using a photoaffinity labeling technique. The results confirm pharmacological observations of the three antagonists that had been proposed to interact allosterically with each other. We briefly review the results and discuss the future prospects.

Affinity Labels↗

PubMed1996

Block of high-threshold calcium channels by the synthetic polyamines sFTX-3.3 and FTX-3.3.

A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain. Consequently, this component has frequently been used as a pharmacological tool to determine the presence, distribution, and function of P-type channels in physiological systems. We describe antagonism of calcium channels by the synthesized polyamine FTX-3.3, which has the proposed structure of natural FTX. We also examined a corresponding polyamine amide, sFTX-3.3. These polyamines are critically evaluated for antagonism of three high-threshold calcium channel subtypes in rat neurons through the use of the whole-cell patch-clamp technique. FTX-3.3 (IC50 = approximately 0.13 mM) is approximately twice as potent as sFTX-3.3 (IC50 = approximately 0.24 mM) against P-type channels and approximately 3-fold more potent against N-type channels (FTX-3.3, IC50 = approximately 0.24 mM; sFTX-3.3, IC50 = approximately 0.70 mM). Both polyamines also block L-type calcium channels with similar potencies. sFTX-3.3 (1 mM) and FTX-3.3 (0.5 mM) typically block 50% and 65% of Bay K8644-enhanced L-type current, respectively. Antagonism of each calcium channel subtype is voltage dependent, with less inhibition of Ba2+ currents at more-positive potentials. These data show that both sFTX-3.3 and FTX-3.3 antagonize P-, N-, and L-type calcium channels in mammalian Purkinje and superior cervical ganglia neurons with similar IC50 values.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

Voltage-dependent calcium channels--beyond dihydropyridine antagonists.

The blockade of L-type calcium channels by dihydropyridines, phenylalkylamines and benzothiazepines has been well described and forms the basis of a multibillion dollar market for the treatment of cardiovascular disease and migraine. More recently, neuron-specific calcium channels have become the subject of intense interest regarding their potential as therapeutic targets for the treatment of chronic and neuropathic pain. A number of recently described agents that selectively target neuronal calcium channels have been described and appear promising for a variety of pain conditions.

Animals↗

PubMedDate not supplied

[Effects of the monosaccharide derivative 8RN-DAGal on the putative P-type calcium channel expressed in Xenopus oocytes].

P-type calcium channels are expressed in Xenopus oocytes after injection of rat cerebellar mRNA. The FTX and omega-Aga-IVa toxins extracted from Agelenopsis aperta venom are known to inhibit the activity of this channel. The present results demonstrate that 8RN-DAGal is also a antagonist of P-type calcium channels. The inhibition of the current, obtained with Ba2+, as charge carrier, is voltage dependent.

Animals↗

PubMedDate not supplied

Calcium channel antagonists in the treatment of coronary artery disease: fundamental pharmacological properties relevant to clinical use.

Calcium channel antagonists are a diverse group of drugs with clinical antianginal and antihypertensive properties. They have as a common property the capacity to lessen the rate of calcium ion entry through a specific type of calcium channel, namely the voltage-gated L-type channel. They do not bind to all the pore molecules; therefore, there is still some residual entry of calcium ions. Variables determining the clinical efficacy of the different drugs include the binding sites involved, the tissue specificity of the drug, the duration of action, and (closely related) the degree of counter-regulatory neurohumoral activation. Inhibitory effects on the calcium channels of vascular smooth muscle explain the antihypertensive effect and the reduction of afterload, one of the antianginal mechanisms common to all of the drugs. In general, the dihydropyridines, such as nifedipine, are more vascular-selective than the non-dihydropyridines, such as verapamil and diltiazem. The latter owe part of their antianginal activity to more prominent effects on the calcium channels in the sinoatrial node (decreased heart rate) and the myocardium (negative inotropic effect). In addition, calcium channel antagonists are coronary artery vasodilators. Whether the latter effect confers on these drugs any specific advantage in the therapy of anginal syndromes is controversial.

Angina Pectoris↗

PubMed2002

Syntheses, calcium channel agonist-antagonist modulation activities, nitric oxide release, and voltage-clamp studies of 2-nitrooxyethyl 1,4-dihydro- 2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate enantiomers.

The novel (-)-(S)-2 and (+)-(R)-3 enantiomers of 2-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate were synthesized for evaluation as calcium channel modulators. Determination of their in vitro calcium-channel-modulating activities using guinea pig left atria (GPLA) and ileum longitudinal smooth muscle (GPILSM) showed that the (-)-(S)-2 enantiomer acted as a dual cardioselective calcium channel agonist (GPLA)/smooth muscle selective calcium channel antagonist (GPILSM). In contrast, the (+)-(R)-3 enantiomer exhibited calcium channel antagonist activity on both GPLA and GPILSM. The 2-nitrooxyethyl racemate is a nitric oxide (.NO) donor that released 2.7% .NO, relative to the reference drug glyceryl trinitrate (5.3% .NO release/ONO(2) moiety), in the presence of N-acetylcysteamine. Whole-cell voltage-clamp studies using isolated guinea pig ventricular myocytes indicated that both enantiomers inhibit calcium current but that the (-)-(S)-2 enantiomer is a weaker antagonist than the (+)-(R)-3 enantiomer. These results indicate that replacement of the methyl ester substituent of (-)-(S)-methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate [(-)-(S)-1] by the 2-nitrooxyethyl ester .NO donor substituent present in (-)-(S)-2 provides a useful drug design concept to abolish the contraindicated calcium channel agonist effect of (-)-(S)-1 on vascular smooth muscle. The novel (-)-(S)-2 enantiomer is a useful lead compound for drug discovery targeted toward the treatment of congestive heart failure, and it provides a useful probe to study the structure-function relationships of calcium channels.

Animals↗

PubMed2004

Applied field nonequilibrium molecular dynamics simulations of ion exit from a beta-barrel model of the L-type calcium channel.

We present results of applied field nonequilibrium molecular dynamics simulations (AF NEMD) of a minimal beta-barrel model channel intended to represent an L-type calcium channel that suggests a possible relationship between glutamate side chain conformational changes and ion flux in calcium channels. The beta-barrel is used to provide a scaffolding for glutamate side chains and a confinement for electrolyte of dimensions similar to the expected channel structure. It was preloaded with ions to explore relative rates of ion exit for different occupancy configurations. Our simulations with an asymmetrical flexible selectivity filter represented by four glutamate side chains (EEEE), one of which differs in initial dihedrals from the other three, indicate a plausible mechanism for the observed anomalous mole fraction effect seen in calcium channels. Apparent rates of electric field-induced exit from channels preloaded with three Na+ ions are much higher than for channels with one Ca2+ followed by two Na+ ions, consistent with the common notion that Ca2+ block of Na+ current is due to competition between the Ca2+ and Na+ ions for the negatively charged (EEEE) locus. In our model, the Ca2+ ion ligates simultaneously to the four negatively charged glutamate side chains and sterically blocks the permeation pathway. Ca2+-relief of Ca2+-block is suggested by a much higher rate of exit for channels preloaded with three Ca2+ ions than for channels with two Ca2+ ions.

Algorithms↗

PubMed1999

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.

Amino Acid Sequence↗

PubMed1993

Calcium-channel blockers and gastrointestinal motility: basic and clinical aspects.

Several calcium-channel blockers currently in use for the treatment of cardiovascular disorders have recently been tested for their effects on gastrointestinal motility. The rationale for this approach centers on the concept that calcium-channel blockers are at least as potent in inhibiting intestinal smooth muscle as in relaxing vascular smooth muscle. This review will give an outline of the most recent findings on the role of calcium and calcium channels in smooth muscle and neuronal function in the digestive system. It will also consider the mechanisms by which calcium-channel blockers may affect gastrointestinal motility and assess potential clinical applications in gastroenterology. The main goal for researchers in this field will be the development of gut-selective agents, with no cardiovascular side effects.

Animals↗

PubMed1989

Characterization of calcium channels of a glucose-responsive rat insulinoma.

Voltage-dependent calcium channels are important in the control of calcium influx into excitable cells. With the use of cells isolated from a glucose-responsive rat insulinoma, the effect of the calcium-channel blocker nitrendipine on insulin release was examined. When 50 nM nitrendipine was added with a stimulatory glucose concentration (30 mM), first-phase insulin release was preserved, whereas the second phase was inhibited by 39.4 +/- 5.3%. When 50 nM nitrendipine was also present during basal and stimulated insulin release, the insulin release from fresh cells was significantly less during both phases compared with cells not exposed to nitrendipine (P less than 0.05). In cells cultured for 1 day in 30 mM glucose, a diminished insulin response was seen on stimulation with 30 mM glucose. Nitrendipine (50 nM) did not lead to a further decrease in insulin release. Saturable binding sites in homogenate, whole cells, and purified plasma membranes prepared from the insulinoma were characterized using [3H]nitrendipine. The Kd (in pM) for homogenate from uncultured cells was 225 +/- 34 (n = 11), whereas the Bmax (in fmol/mg protein) was 52 +/- 5. The number of apparent binding sites for [3H]nitrendipine was reduced by approximately 50% in cultured cells (Bmax = 30 +/- 5 fmol/mg protein). The reduction in insulin release from cultured cells correlated well with the reduction in nitrendipine binding. It is concluded that the decrease in the number of apparent binding sites for nitrendipine after culture represents a reduction in functional calcium channels associated with influx of calcium and insulin release.

Adenoma, Islet Cell↗

PubMed1987

Calcium channel currents and their inhibition by (-)-baclofen in rat sensory neurones: modulation by guanine nucleotides.

1. The effect of intracellular application of the hydrolysis-resistant GTP and GDP analogues, guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S), and guanosine 5'-O-2-thiodiphosphate (GDP-beta-S) has been examined on voltage-activated calcium-channel currents and the ability of the gamma-aminobutyric acid B agonist baclofen to inhibit them, in cultured rat dorsal root ganglion (d.r.g.) neurones. 2. Under control conditions, the calcium-channel current, recorded using the whole-cell patch technique with Ba2+ rather than Ca2+ as the permeant divalent cation, consists of an inactivating and a sustained current. In the presence of 500 microM-GTP-gamma-S included in the patch pipette, the calcium-channel current was activated more slowly and was largely non-inactivating during the 100 ms depolarization voltage step. The effects of GTP-gamma-S were abolished by pre-treatment of cells with pertussis toxin. 3. The calcium-channel current recorded in the presence of 500 microM-GDP-beta-S had a more marked transient component than the control calcium-channel current. The proportion of transient calcium-channel current in the presence of GDP-beta-S was not reduced in Na+-free medium. 4. No statistically significant effects of GTP-gamma-S and GDP-beta-S were observed on the calcium-activated potassium current IK(Ca), the transient outward potassium current activated in Ca2+-free medium, or on the inwardly rectifying current (Ih) activated by hyperpolarization. 5. GTP-gamma-S increased the ability of baclofen to inhibit calcium-channel currents, whereas this was decreased by GDP-beta-S and by pre-treatment of cells with pertussis toxin. The half-maximal effective dose (EC50) for baclofen was 2 microM in the presence of GTP-gamma-S, 15 microM for control and 50 microM in the presence of GDP-beta-S. Comparable results were obtained using a single concentration of the adenosine agonist 2-chloroadenosine (2-CA, 0.05 microM) to inhibit calcium-channel currents; its effect was significantly increased by GTP-gamma-S and reduced by GDP-beta-S. 6. The ability of baclofen to inhibit calcium-channel currents was not affected by 1 microM-forskolin or 50 microM-intracellular cyclic AMP. 7. It is concluded that calcium channels in d.r.g.s are associated with a nucleotide binding protein, and that this mediates the effect of baclofen and 2-CA on calcium-channel currents. The ability of GTP-gamma-S to inhibit the transient component of calcium-channel currents in the absence of agonist may represent a means of differentially regulating calcium-channel activity.

Action Potentials↗

PubMed2000

Calcium channel antagonist effect on in vitro meningioma signal transduction pathways after growth factor stimulation.

OBJECTIVE: We have previously demonstrated that calcium channel antagonists inhibit the growth of human meningiomas in culture after stimulation with growth factors. This study examined the effects of these drugs on signaling transduction pathways in an attempt to elucidate potential mechanisms by which this growth inhibition is mediated. METHODS: Primary cell cultures from patients with intracranial meningiomas were established. Cell growth studies were performed with inhibitors and stimulators of tyrosine kinase signal transduction. Intracellular calcium changes and inositol phosphate production were measured after growth factor exposure, with or without pretreatment by calcium channel antagonists. RESULTS: The growth of meningiomas in culture can be inhibited by tyrosine kinase receptor inhibitors. Inhibitors and stimulators of phospholipase C can stimulate or inhibit the growth of in vitro meningiomas, respectively. Calcium channel antagonists inhibit intracellular calcium changes induced by serum and epidermal growth factor. Inositol phosphate production is increased after growth factor stimulation, and calcium channel antagonists potentiate this effect. CONCLUSION: Calcium channel antagonists interfere with intracellular signaling pathways of cultured meningioma cells. This inhibition is unrelated to voltage-sensitive calcium channels. The findings of this project may aid in the understanding of the signal transduction mechanisms involved in growth factor-mediated meningioma proliferation and may lead to clinically relevant strategies for growth inhibition.

Adult↗