The inhibition of the inositol 1,4,5-trisphosphate receptor from rat cerebellum by spermine and other polyamines

Abstract

Inositol 1,4,5-trisphosphate-induced Ca2+ release from rat cerebellar microsomes can be inhibited by polyamines at mM concentrations. Spermine, one of the most abundant naturally occurring polyamines, inhibits InsP3-induced Ca2+ release with an IC50 of 1 mM. However, the antibiotic neomycin proved most efficacious at inhibiting InsP3-induced Ca2+ release (IC50 0.4mM). The order of potency being neomycin > spermine > spermidine > putrescine. Although binding of [3H]InsP3 to cerebellar microsomes is also inhibited by polyamines, this may be due to InsP3 complexing with the polyamines under the binding conditions used. Under Ca2+ release conditions InsP3 binds weakly to spermine and therefore inhibition of InsP3-induced Ca2+ release is consistent with polyamines interacting with the InsP3 receptor.