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Release of norepinephrine and dopamine from brain vesicular preparations: Effects of calcium antagonists

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Summary

  1. 1.

    The calcium antagonists D-600 (1–10µM) and diltiazem (10–25µM) inhibit K+-evoked release of [3H]norepinephrine from guinea pig cerebral cortical vesicular preparations. The inhibition of release is partially reversed by increasing concentrations of calcium to 2 mM. Diltiazem at 100µM has no effect on K+-evoked release of [3H]norepinephrine at 0.15 mM calcium but does inhibit release at 2.0 mM calcium.

  2. 2.

    The calcium antagonist nifedipine and dantrolene, an agent purported to antagonize release of calcium from intracellular storage sites, have no effect on K+-evoked release of [3H]norepinephrine.

  3. 3.

    The calcium antagonists D-600 (1µM) and diltiazem (10µM) inhibit K+-evoked release of [3H]dopamine from guinea pig striatal vesicular preparations. Higher concentrations of drug, namely, 10µM for D-600 and 100µM for diltiazem, cause a potentiation rather than an inhibition of K+-evoked release. The potentiation is reduced in magnitude upon raising the extracellular calcium to 2.0 mM. Indeed, 10µM D-600 then inhibits K+-evoked release of [3H]dopamine.

  4. 4.

    The results indicate that putative calcium antagonists can have both inhibitory and facilitory effects on calcium-dependent K+-evoked release of catecholamines from central synaptic endings. Furthermore, certain peripheral calcium antagonists such as nifedipine and dantrolene may prove ineffective in central systems.

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Author notes

  1. Richard P. Ebstein

    Present address: Jerusalem Mental Health Center, P.O.B. 140, Jerusalem, Israel

Authors and Affiliations

  1. Laboratory of Bioorganic Chemistry, National Institute of Arthritis, Diabetes, and Digestive and Kidney Disease, National Institutes of Health, 20205, Bethesda, Maryland, USA

    Richard P. Ebstein & John W. Daly

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  1. Richard P. Ebstein
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  2. John W. Daly
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Ebstein, R.P., Daly, J.W. Release of norepinephrine and dopamine from brain vesicular preparations: Effects of calcium antagonists. Cell Mol Neurobiol 2, 205–213 (1982). https://doi.org/10.1007/BF00711148

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  • DOI: https://doi.org/10.1007/BF00711148

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