The inhibition of the inositol 1,4,5-trisphosphate receptor from rat cerebellum by spermine and other polyamines.
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.
Sayers
L G
LG
School of Biochemistry, University of Birmingham, Edgbaston, U.K.
Michelangeli
F
F
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002531:Cerebellum / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011073:Polyamines; D018160:Receptors, Cytoplasmic and Nuclear; D013096:Spermine; D000001:Calcimycin; D015544:Inositol 1,4,5-Trisphosphate; D009355:Neomycin; D002118:Calcium; D013095:Spermidine; D011700:Putrescine