Calciseptine Binding to a 1,4-Dihydropyridine Recognition Site of the L-Type Calcium Channel of Rat Synaptosomal Membranes

Yasuda, Osamu; Morimoto, Shigeto; Chen, Yuehao; Jiang, Bin; Kimura, Terutoshi; Sakakibara, Shunsuke; Koh, Eio; Fukuo, Keisuke; Kitano, Shigeru; Ogihara, Takuo

doi:10.1006/bbrc.1993.1862

Cited by 33 publications

(14 citation statements)

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“…This was supported by the finding that CaS in the bath had no effect on the activity of unitary currents in the cell-attached membrane patch. These results are consistent with previous observations that the DHP-binding site is located on the outer side of the membrane [12,13,16], if we assume that CaS competitively acts on the DHP-binding site [20].…”

Section: Discussionsupporting

confidence: 93%

“…Thus, CaS seems to act on the outer membrane side of Cat channels in the guinea-pig portal vein. Although the present experiments provide no direct evidence for the site of action of CaS in relation to the DHP-binding site, it has been reported that it replaces nitrendipine at its specific binding site in rat synaptosomes and that, in concentrations of up to 10 nM, had no effect on w-conotoxin binding sites [20]. In the present experiments, although we did not try the binding experiments, Bay K 8644 seemed to antagonize the inhibitory actions of CaS on the spontaneous contraction.…”

Section: Discussioncontrasting

confidence: 82%

“…It has been reported to be a selective L-type Cat channel blocker, because it has no effect on the T-and N-type Cat channels in cardiac and neuronal cells [2,19]. CaS has also been reported to competitively inhibit nitrendipine binding to its specific binding site in rat synaptosomal membranes [20]. In smooth muscle cells, this toxin has been shown to inhibit action potentials and the Caz+ inward current in A7r5 cells; it has also been shown to inhibit contractions induced by excess K+ and spontaneously generated contractions in vascular smooth muscle preparations and to have hypotensive effects in the anesthetized rat [2,19].…”

Section: Introductionmentioning

confidence: 99%

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Effects of calciseptine on unitary barium channel currents in guinea-pig portal vein

Teramoto

Ogata

Kuriyama

et al. 1996

Pflugers Arch - Eur J Physiol

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Effects of synthesized calciseptine (CaS), found naturally in the venom of the black mamba, on voltage-dependent Ca2+ channels in smooth muscle cells of the guinea-pig portal vein were investigated. In the whole-cell voltage-clamp configuration, extracellular application of CaS (>/= 10 nM) inhibited the inward current in a concentration- and voltage-dependent manner at a holding potential of -90 mV. The Ca2+ current recorded at a high holding potential (-50 mV) was approximately 8 times more sensitive to CaS than that at a more negative holding potential (-90 mV). CaS (50 nM) shifted to the left the steady-state inactivation curve obtained by using single 8-s conditioning pulses of various amplitudes. When CaS (>/= 200 nM) was present in the pipette, the Ca2+ current remained for the duration of the experiments (more than 60 min) in the whole-cell configuration. Two different Ca2+ channel conductances are present in this tissue (25-pS and 12-pS channels). Both channels are blocked by dihydropyridine (DHP) derivatives, but have different sensitivities. In the cell-attached condition, CaS hardly changed the activity of either unitary Ca2+ channel current. To prevent the "run down" of the Ca2+ channels in cell-free conditions, we added cardiac cytosol, a supernatant from homogenized cardiac cells and an endogenous Ca2+ channel activating factor, in the pipette. The unitary Ca2+ channel currents were then recorded using the outside-out membrane patch configuration. Application of CaS (1 microM) in the bath completely blocked the open events of the 25-pS Ca2+ channel. CaS (10 nM) in the bath reduced the mean open time and channel availability, resulting in a decrease in the open probability of the 25-pS channel currents without affecting the amplitude of the single-channel conductance. CaS also reduced the open probability (though less potently) and channel availability of the 12-pS Ca2+ channel without a change in its amplitude. From these results, we conclude that CaS has inhibitory effects on the voltage-dependent Ca2+ current that are similar to those of DHP derivatives and that it acts from the outside of the membrane.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Effects of calciseptine on unitary barium channel currents in guinea-pig portal vein

Teramoto

Ogata

Kuriyama

et al. 1996

Pflugers Arch - Eur J Physiol

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“…Its relaxing activities were similar to those of nifedipine in various in vitro and in vivo preparations. Our synthetic calciseptine binds to a 1,4-dihydropyridine recognition site of the Ltype Ca" channel in rat synaptosomal membranes (17). These data demonstrated that synthetic calciseptine is a specific inhibitor of L-type Ca" channels.…”

Section: Inhibiting Activities On Ach Contraction In Ileummentioning

confidence: 60%

Smooth Muscle Relaxing and Hypotensive Activities of Synthetic Calciseptine and the Homologous Snake Venom Peptide FS2

Watanabe

Itahara

Kuroda

et al. 1995

Japanese Journal of Pharmacology

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“…To test this hypothesis, nerve muscle preparations were treated with L-type channel blockers that lack any potentiation effect per se before nifedipine. We used the high-affinity DHP isradipine (Scholze et al, 2001) and calciseptine, which interact with the channel at the same site as DHPs, but are membrane-impermeable (Yasuda et al, 1993). Neither calciseptine nor low or high concentrations of isradipine were capable of preventing the strong increase (over 50-fold) of MEPP frequency exerted by nifedipine (Fig.…”

Section: Resultsmentioning

confidence: 99%

Nifedipine-Mediated Mobilization of Intracellular Calcium Stores Increases Spontaneous Neurotransmitter Release at Neonatal Rat Motor Nerve Terminals

Piriz¹,

Siri²,

Pagani³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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The modulation of spontaneous release of acetylcholine by specific Ca 2ϩ channel blockers was studied at neonatal rat neuromuscular junction. During early postnatal periods (0 -4 days), blockers of N-and P/Q-type Ca 2ϩ channels did not affect miniature endplate potential (MEPP) frequency. Unexpectedly, treatment with the L-type Ca 2ϩ channel antagonist nifedipine, although not when treated with isradipine, nitrendipine, or calciseptine, resulted in strong increase in MEPP frequency. The potentiation effect of nifedipine was dose-dependent with a 56-fold maximum effect with 15 M. The effect decreased during the first two postnatal weeks and disappeared by the third. The effect of nifedipine was not dependent on extracellular Ca 2ϩ and was not altered by the presence of other Ca 2ϩ channel blockers. In contrast, it was abolished by depleting intracellular Ca 2ϩ stores with 2 M thapsigargin and was partially inhibited by 10 M ryanodine. In conclusion, we report a new ryanodine receptor-mediated effect of nifedipine on neonatal neuromuscular junction that may indicate the developmental expression of a specific receptor channel that interacts with intracellular Ca 2ϩ stores. This effect of nifedipine should also be considered when using this drug as either a therapeutic or a research tool.

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Calciseptine Binding to a 1,4-Dihydropyridine Recognition Site of the L-Type Calcium Channel of Rat Synaptosomal Membranes

Cited by 33 publications

References 0 publications

Effects of calciseptine on unitary barium channel currents in guinea-pig portal vein

Effects of calciseptine on unitary barium channel currents in guinea-pig portal vein

Smooth Muscle Relaxing and Hypotensive Activities of Synthetic Calciseptine and the Homologous Snake Venom Peptide FS2

Nifedipine-Mediated Mobilization of Intracellular Calcium Stores Increases Spontaneous Neurotransmitter Release at Neonatal Rat Motor Nerve Terminals

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