Inhibition of high affinity synaptosomal uptake systems by verapamil

R. McGee, J. E. Schneider

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Verapamil and its analogue D-600 have been found to inhibit the uptake of serotonin, dopamine, norepinephrine and choline into rat forebrain synaptosomes. The concentrations of verapamil required for 50% inhibition of the four uptake systems were 2.3 μM, 18μM, 32μM and 150μM, respectively. The inhibitory effect of verapamil on serotonin uptake was studied in detail and found to have a very rapid (less than 1 min) time of onset and an almost equally rapid rate of reversal. Inhibition appeared to be non-competitive with respect to substrate concentration. The inhibitory effects of verapamil did not seem to be due to its ability to block Ca++ movements since serotonin uptake was not dependent on Ca++ but actually inhibited by elevated Ca++, and the inhibition of uptake by verapamil could not be reversed by elevation of Ca++. However, due to an increased potency of verapamil at lowered Na+ concentrations, the Na+-dependency of the uptake processes, and verapamil's known effects on 'slow' Na+ currents, we propose that verapamil may be interfering with a Na+-dependent component of the uptake systems.

Original languageEnglish (US)
Pages (from-to)877-885
Number of pages9
JournalMolecular Pharmacology
Volume16
Issue number3
StatePublished - Dec 1 1979

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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