Evidence for down-regulation of 3H-nitrendipine recognition sites in mouse brain after long-term treatment with nifedipine or verapamil

Panza, Gregory A.; Grebb, Jack A.; Sanna, Enrico; Wright, A. G.; Hanbauer, Ingeborg

doi:10.1016/0028-3908(85)90200-x

Cited by 68 publications

(17 citation statements)

References 4 publications

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“…Panza et al [5] showed a down-regulation in the number o f [2H]nitrendipine binding sites in membranes prepared from mouse brain tissue after long-term oral administration (28 days) with nifedipine (280 mg/kg/day) and verapamil (270 mg/kg/day) but not with diltiazem (380 mg/kg/day). A down-regulation in the number o f brain and cardiac C a 2+ channels was shown by Gengo et al [6] in rats receiving chronic intravenous administration o f nifedi pine (0.864 and 8.640 mg/kg/day) for 20 days.…”

Section: Discussionmentioning

confidence: 99%

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Effect of High-Dose Verapamil Administration on the Ca<sup>2+</sup> Channel Density in Rat Cardiac Tissue

et al. 1994

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It is well known that β-adrenergic receptors will down-regulate in the presence of high circulating levels of β-adrenergic agonists over extended periods of time. However, less is known with respect to the effect of Ca²⁺ channel antagonists on their receptors. The purpose of this study was to determine if chronic administration of high dosages of verapamil (in the toxic range) could alter the density of Ca²⁺ channels in the heart as determined by [³H]PN 200-110 binding. A range of high verapamil concentrations was administered to rats via s.c. implantable slow-release pellets or s.c. injection. An increasing rate of mortality was observed as the dose of verapamil administered increased. Quantitation of serum verapamil concentrations demonstrated that the s.c. slow release implantable pellets were not releasing the drug evenly and instead released toxic quantities of drug during the first 24 h after implantation. Serum verapamil levels determined from verapamil-injected animals demonstrated a dose-dependent increase in circulating levels. No significant alterations in Ca²⁺ channel characteristics (B_max and K_d) were noted in cardiac tissue obtained from either treatment regime. Our results demonstrate that implantable pellets are not a reliable administration method for verapamil and cardiac Ca²⁺ channels are unusually resistant to biochemical alterations even after administration of verapamil dosages in the toxic range.

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Section: Discussionmentioning

confidence: 99%

“…A reduction in the number o f brain C a 2+ channels in mice [5] and rats [6] were observed after >20 days o f admin istration o f nifedipine or verapamil. However, the data in heart tissue is more controversial.…”

Section: Introductionmentioning

confidence: 99%

Effect of High-Dose Verapamil Administration on the Ca<sup>2+</sup> Channel Density in Rat Cardiac Tissue

et al. 1994

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“…We suggest therefore that the effects of chronically administered nitrendipine were due to an adaptive response to the presence of the compound in the central nervous system, preventing the action of ethanol on the dihydropyridinesensitive channels. Panza et al (1985) demonstrated that the long term intake of a dihydropyridine calcium channel antagonist could result in down-regulation of central dihydropyridine-sensitive binding sites. This study used considerable higher doses (280mgkg-1 daily) than the present experiments.…”

Section: Discussionmentioning

confidence: 99%

Nitrendipine, given during drinking, decreases the electrophysiological changes in the isolated hippocampal slice, seen during ethanol withdrawal

Whittington¹,

Little²

1991

British J Pharmacology

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1 Extracellular recordings were made from mouse isolated hippocampal slices prepared after chronic treatment in vivo with either ethanol or ethanol plus the dihydropyridine calcium channel antagonist, nitrendipine. 2 The withdrawal of ethanol caused a variety of changes in the field potentials, as previously reported, including decreases in the thresholds for eliciting single and multiple population spikes, increases in paired pulse potentiation and shifts to the left of the input/output curves. 3 The addition of nitrendipine to the drinking mixture in the chronic ethanol treatment significantly decreased all the changes in the field potentials that were seen after ethanol withdrawal. 4 Addition of nitrenedipine to the perfusion medium also decreased the signs of hyperexcitability seen in the hippocampal slices during ethanol withdrawal. 5The results provide further evidence that neuronal calcium channels may be involved in ethanol dependence and that the adaptive changes caused by chronic ethanol treatment can be modulated by alterations at dihydropyridine-sensitive sites.

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“…When given chronically with ethanol, this dihydropyridine prevented the electrophysiological and behavioural manifestations of ethanol withdrawal. We have suggested that this latter effect is due to an adaptive response, decreasing the number of dihydropyridine binding sites, as shown by Panza et al (1985) and opposing the increase in the number of these sites that is caused by chronic ethanol (Whittington et al, 1991). We have now studied the actions of racemic PN 200-110 when this compound is given by the chronic treatment schedule that we found to be effective in our ethanol studies.…”

Section: Ars Is a Glaxo Research Scholarmentioning

confidence: 99%

Poster Communications

1991

British J Pharmacology

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Evidence for down-regulation of 3H-nitrendipine recognition sites in mouse brain after long-term treatment with nifedipine or verapamil

Cited by 68 publications

References 4 publications

Effect of High-Dose Verapamil Administration on the Ca<sup>2+</sup> Channel Density in Rat Cardiac Tissue

Effect of High-Dose Verapamil Administration on the Ca<sup>2+</sup> Channel Density in Rat Cardiac Tissue

Nitrendipine, given during drinking, decreases the electrophysiological changes in the isolated hippocampal slice, seen during ethanol withdrawal

Poster Communications

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