Ryanodine receptor modulation by diadenosine polyphosphates in synaptosomal and microsomal preparations of rat brain

P. Nickolas Shepel, Clark P. Holden, Jonathan D. Geiger

Research output: Contribution to journalArticle

2 Scopus citations


Diadenosine polyphosphates (ApnAs) are transmitter-like substances that act intracellularly via unclear mechanisms. Here we tested hypotheses that diadenosine tetraphosphate (Ap4A) modulates ryanodine binding in microsomal and synaptosomal fractions of rat brain, and that Ap4A affects modulation of ryanodine binding by divalent cations and caffeine. Using [3H]ryanodine-binding assays, we showed that Ap4A produced significant and concentration-dependent increases in [3H]ryanodine binding in microsomes and these actions were reduced by Mg2+ and potentiated by caffeine. In synaptosomal subfractions, effects of Ap4A on [3H]ryanodine binding were most profound in subfractions enriched in synaptic vesicle-associated protein synaptophysin. These results suggest that ApnAs and ryanodine receptors are well placed to modulate Ca2+-dependent synaptic processes.

Original languageEnglish (US)
Pages (from-to)67-71
Number of pages5
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - Apr 25 2003



  • Dinucleotide oxidized
  • GRP-78
  • Subcellular fractionation
  • Synaptophysin

ASJC Scopus subject areas

  • Pharmacology

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