On the specificity of verapamil as a calcium channel-blocker

Norris, D.K.; Bradford, H. F.

doi:10.1016/0006-2952(85)90314-4

Cited by 23 publications

(7 citation statements)

References 19 publications

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“…The verapamil concentrations achieved in our experiments can be calculated to be 8-16 mg/100 ml or 200-400 umol/liter. This is well above the concentration where verapamil changes from a specific calcium antagonist to a sodium channel blocker (39). Thus, we cannot exclude that nonspecific membrane effects of verapamil were contributing to our results.…”

Section: Resultsmentioning

confidence: 79%

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Reichen¹,

Le²

1986

J. Clin. Invest.

131

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The effect of the calcium channel blocking agent, verapamil, on microcirculatory patterns and hepatic function was investigated in the perfused liver of cirrhotic rats. Compared with controls, cirrhotic livers had higher vascular resistance, increased intrahepatic shunting, and smaller extravascular albumin space and larger extravascular sucrose space, as determined by a multipleindicator dilution technique. Hepatic function, estimated by determining propranolol and antipyrine extraction, was markedly reduced in cirrhotic livers. Portal pressure was then reduced 25% either pharmacologically by verapamil or hydrodynamically by lowering inflow. Verapamil decreased vascular resistance by 22%. This was associated with a 38% reduction in intrahepatic shunting and a 62% increase in extravascular albumin space. Hydrodynamically lowering pressure had no or adverse effects. The verapamil-induced improvement in microcirculatory characteristics was associated with a significant improvement in oxygen consumption (+21%) and antipyrine clearance (+20%). We conclude that the microvascular distortions of liver cirrhosis in the rat are partially reversible by vasodilators like verapamil.

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Section: Resultsmentioning

confidence: 79%

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Reichen¹,

Le²

1986

J. Clin. Invest.

131

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“…In the present study, 'brain dialysis' enabled us to measure the extracellular Ca2 + changes and transmitter (glutamate) (Norris & Bradford, 1985;Mody & Heinemann, 1986) and Ca2+ influx stimulated by veratridine and KCl proved to be mediated by VSCC (Nachshen & Blaustein, 1979). Moreover, Ca2+ influx by glial cells is not an important site for Ca2 + fluxes induced by these depolarizing agents and excitotoxins (Kelly & Krnjevic, 1967;Bowman & Kimelberg, 1984).…”

Section: Discussionmentioning

confidence: 89%

Effects of Ca²⁺antagonists on glutamate release and Ca²⁺influx in the hippocampus with in vivo intracerebral microdialysis

Lü

Zhang

Zhao

et al. 1991

British J Pharmacology

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1The extracellular glutamate content and Ca2+ level in vivo in rat hippocampus were measured by brain microdialysis following administration of two depolarizing agents (veratridine, KCl) and quinolinic acid (Quin). 2 The two depolarizing agents increased the extracellular glutamate level (to between 280 and 320% basal) and decreased the extracellular Ca2" content (to 48% of basal). However, Quin did not change the glutamate level but decreased the Ca2+ content. 3 The effects of Ca2+ antagonists on the changes of glutamate and Ca2+ level were evaluated in this experimental model. At a dose of 0.5 mgkg-1, i.v., nimodipine (L-type channel blocker) did not produce significant changes in the stimulated-glutamate release. A statistically significant inhibition of Ca2 + influx was observed at a dose of 0.05 mg kg'-. In contrast, in those animals receiving the N-type Ca2 + antagonist, daurisoline (0.1, 1 or 5 mg kg ',i.v.), a potent attenuation of both glutamate release and Ca2 + influx was found. 4 We propose that the pharmacological properties of Ca2 + influx and of neurotransmitter release differ and that nimodipine-sensitive L-type channels may not be very common in nerve terminals but are localized in cell soma. Daurisoline-sensitive N-type channels in nerve terminals have a much greater influence on excitatory amino acid release.

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“…Dagani et al [4] showed that stimulation of synaptosomal ox ygen consumption induced by veratridine was not altered by diltiazem in the concen tration range that we used. Finally, Norris and Bradford [7] also observed that vera pamil at a concentration up to 10 pmol/1 did not interfere with excessive Na fluxes.…”

Section: Effects O F Ca Antagonists On Veratridine-induced Na Influxmentioning

confidence: 82%

“…Therefore, attenuation of the high Na conductance during ischaemia may also have a beneficial effect. In order to verify whether some Ca channel blockers derive their protective action, at least partly, from an antagonism of Na channels [7][8][9], we developed a simple method to identify compounds interfering with excessive Na in fluxes. Methods currently available for this purpose require the use of either 22Na [10,11] or Na+-sensitive micro-electrodes [12], which makes them unsuitable for screening a large number of drugs.…”

Section: Introductionmentioning

confidence: 99%

Synaptosomal Respiration: A Potent Indicator of Veratridine-Induced Na Influx

Urenjak¹,

Tegtmeier²,

Beile³

et al. 1991

Pharmacology

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Inhibition of the voltage-dependent Na channel by tetrodotoxin (5 μmol/l) decreased by about 86% the stimulation of the respiration of rat brain synaptosomes induced by veratridine (10 μmol/l). A similar effect was achieved by blocking Na⁺-K⁺-ATPase with ouabain (1 mmol/l). Pharmacological manipulations of Ca homeostasis suggested that the veratridine-induced stimulation of respiration did not depend upon Ca entry. These data suggest that the veratridine-induced stimulation of synaptosomal respiration may result primarily from an increase in intracellular Na⁺. They provide the basis for an indirect method, which only requires recording of synaptosomal respiration, to test drugs for their possible interaction with excessive Na influxes.

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On the specificity of verapamil as a calcium channel-blocker

Cited by 23 publications

References 19 publications

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Effects of Ca²⁺antagonists on glutamate release and Ca²⁺influx in the hippocampus with in vivo intracerebral microdialysis

Synaptosomal Respiration: A Potent Indicator of Veratridine-Induced Na Influx

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On the specificity of verapamil as a calcium channel-blocker

Cited by 23 publications

References 19 publications

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Effects of Ca2+antagonists on glutamate release and Ca2+influx in the hippocampus with in vivo intracerebral microdialysis

Synaptosomal Respiration: A Potent Indicator of Veratridine-Induced Na Influx

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Effects of Ca²⁺antagonists on glutamate release and Ca²⁺influx in the hippocampus with in vivo intracerebral microdialysis