Interaction of calcium channel blockers with non-neuronal benzodiazepine binding sites.

Cantor, Elinor H.; Kenessey, Ágnes; Semenuk, G.; Spector, Sydney

doi:10.1073/pnas.81.5.1549

Cited by 66 publications

(23 citation statements)

References 26 publications

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“…This binding site may be involved in the control of calcium channels [25]. It is known that peripherally acting BZDs inhibit plasma membrane cal cium influx at micromolar concentrations [26,27], Taft and De Lorenzo [27] suggested the existence of the dis tinct 'micromolar' binding site for peripherally acting BZDs, connected with the plasma membrane and regulat ing voltage-sensitive calcium channels. On the other hand, the 'peripheral' BZDs may interact with dihydropy ridine binding sites.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the 'peripheral' BZDs may interact with dihydropy ridine binding sites. Cantor et al [26] have shown that nifedipine, a dihydropyridine calcium channel blocker, displaced the tritiated Ro 5-4864 from the membranes of the heart, kidney and brain. Also, the existence of an endogenous protein, which modifies both 'peripheral' BZDs and dihydropyridine calcium channel antagonist binding sites, has been postulated [28],…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Kunert‐Radek¹,

Stępień²,

Pawlikowski³

1994

Neuroendocrinology

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The effect of various benzodiazepines (peripheral-type receptor ligands: Ro 5-4864, PK 11135; central-type receptor ligands: clonazepam, Ro 15-1788, Ro 15-4513; mixed type: diazepam) on the proliferation of estrogen-induced rat pituitary prolactin-secreting tumor cells was studied in vitro. [³H]thymidine incorporation into DNA was used as an index of cell proliferation. It was found that tested peripheral- and mixed-type benzodiazepine receptor ligands significantly suppressed the pituitary cell proliferation in a dose-dependent manner (10^–4–10^–8M). The inhibitory effect of Ro 5-4864 was reversed by 5 × 10^–3M calcium chloride. On the other hand, central-type benzodiazepine receptor ligands suppressed tumor cell proliferation only at the highest concentration studied (10^–4 M). Our results indicate that benzodiazepines might exert an antiproliferative action on pituitary tumor cell growth, and that this effect seems to be a calcium-dependent process.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Kunert‐Radek¹,

Stępień²,

Pawlikowski³

1994

Neuroendocrinology

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“…When given alone, calcium channel antagonists did not produce general anaesthesia, even at very high doses . Micromolar concentrations of benzodiazepines inhibited [3H]-nitrendipine binding (Bender & Hertz, 1985), and micromolar concentrations of calcium channel antagonists displaced binding at the peripheral benzodiazepine receptor (Cantor et al, 1984). As the concentrations required to produce these effects were well in excess of the Kd values for other receptor ligands, a nonspecific effect is the most likely explanation.…”

Section: Introductionmentioning

confidence: 99%

Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs

Dolin¹,

Patch²,

Rabbani

et al. 1990

British J Pharmacology

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1 The effects of the calcium channel blocking agent, nitrendipine, were studied on seizures in mice produced during withdrawal from chronic benzodiazepine treatment and on the development of tolerance to benzodiazepines. 2 Nitrendipine produced a dose-dependent decrease in seizure incidence, when seizures were produced by the partial inverse agonist FG7142 during withdrawal from seven days treatment with flurazepam. 3 Nitrendipine did not raise the seizure thresholds in naive mice to the full inverse agonist methyl-6,7-dimethoxy-4-ethyl-,8-carboline-3-carboxylate (DMCM), or to the y-aminobutyric acid (GABA) antagonist, 7 These results with benzodiazepines are partially in contrast with those for ethanol, where nitrendipine not only decreased ethanol withdrawal seizures when given acutely, but also prevented the development of tolerance and withdrawal signs when given concurrently with ethanol. However, they do confrm the selectivity of nitrendipine for withdrawal-induced seizures.

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“…Although the site of action of Ro5-4864 remains unclear, there is speculation that its pharmacologic actions may be mediated at the GABA-BDZ receptor complex in the CNS [24,25]. Interaction between Ca++-channel blockers (e.g., nifedipine, nitren dipine) and Ro5-4864 has recently been dem onstrated in brain and other peripheral tis sues [26], and some recent studies have also ascribed several pharmacologic actions of Ro5-4864 to Ca++ antagonism [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Benzodiazepine Receptor Development in Murine Glial Cultures

Talwar

Sher²

1987

Dev Neurosci

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Benzodiazepine (BDZ) receptor binding characteristics were determined from glial cultures prepared from the cerebral hemispheres of newborn mice. Receptor binding and saturation analyses were performed at various ages in culture on intact cells. Utilizing 5 nM³H-diazepam at 0.4°C, specific binding reached a plateau at 16–21 days after plating. A single high-affinity binding site was identified with K_d 25.3 ± 2.6 nM and B_max 7,575 ± 410 fmol/mg protein. Inhibition studies utilizing clonazepam indicated that this ligand, thought to have affinity exclusively for neurons, displaces more than 20% of the specific BDZ binding at concentrations as low as 300 nM, although the IC₅₀ was 1.5–2.0 µM. In contrast, the IC₅₀ for Ro5–4864 was 10–20 nM.

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Interaction of calcium channel blockers with non-neuronal benzodiazepine binding sites.

Cited by 66 publications

References 26 publications

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs

Benzodiazepine Receptor Development in Murine Glial Cultures

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