Physiological and pharmacological correlates of calcium antagonist receptors

John A. Wagner, Ian J. Reynolds, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

We studied voltage-sensitive and Na-dependent Ca2+ flux into synaptosomes as well as Na-dependent influx in cardiac sarcolemmal vesicles. Rapid, voltage-sensitive 45Ca2+ influx into synaptosomes is blocked by cadmium (IC50 1 μM) and the novel peptide toxin ω-conotoxin GVIA (30% of uptake blocked by 50 pM toxin), but not by dihydropyridine and phenylalkylamine calcium antagonists, even though [3H]dihydropyridines and [3H]phenylalkylamines bind to synaptosomes. The toxin also blocks voltage-sensitive neurotransmitter release from synaptosomes. Sodium-dependent Ca2+ flux into synaptosomes and cardiac sarcolemmal vesicles is inhibited by selected antihistamines, neuroleptics, and tricyclic antidepressants. We can elicit neurotransmitter release from synaptosomes by changing the Na gradient; this neurotransmitter release is absolutely Ca2+-dependent and blocked by Na+/Ca2+ exchange inhibitors, thereby suggesting that physiological neurotransmitter release may have a Na+/Ca2+ exchange component. More potent Na+/Ca2+ exchange inhibitors may have cardiovascular roles as inotropic agents or antagonists of calcium-related injury to cardiomyocytes during reperfusion or other disease states.

Original languageEnglish (US)
Pages (from-to)S1-S9
JournalJournal of cardiovascular pharmacology
Volume10
DOIs
StatePublished - 1987

Keywords

  • Benzothiazepine
  • Dihydropyridine
  • Na/Ca Exchange
  • Neurotransmitter release
  • Phenylalkylamine
  • Voltage-sensitive calcium channels

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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