The relationship between inositol trisphosphate receptor density and calcium release in brain microsomes.
Calcium release in response to D-myo-inositol-1,4,5-trisphosphate (IP3) was compared in two microsomal preparations derived from cerebellum and forebrain, regions of the brain that differ greatly in their density of [3H]IP3 binding sites. The proportion of accumulated calcium released by IP3 was the same in both microsomal preparations when a saturating dose of IP3 was used. However, the concentration of IP3 or a nonhydrolyzable analog required to elicit half-maximal release was lower in cerebellum than in forebrain microsomes. Because cerebellum microsomes contain approximately 15 times the binding density of forebrain microsomes, the data suggest that the Ca2+ release response is proportional to the occupancy of IP3 binding sites. This was also demonstrated by the observation that heparin, an inhibitor of IP3 binding, blocked IP3-mediated Ca2+ release from both cerebellum and forebrain microsomes. The potency of heparin was dependent on IP3 concentration and was independent of receptor density. These data support the view that the receptor present in brain membranes represents the ligand-binding domain of a Ca2+ release mechanism.
Joseph
S K
SK
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Rice
H L
HL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis*; D018160:Receptors, Cytoplasmic and Nuclear
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D002118:Calcium