Inositol 1,3,4,5-tetrakisphosphate-induced Ca2+ sequestration into bovine adrenal-medullary secretory vesicles

Abstract

Ins(1,3,4,5)P4 induced a rapid sequestration of Ca2+ into both secretory vesicles and microsomes of bovine adrenal medulla. The Ca2+-sequestering role of Ins(1,3,4,5)P4 contrasts with the Ca2+-releasing role of Ins(1,4,5) P3 in adrenal medullary secretory vesicles and microsomes. The Ins(l,3,4,5) P4-induced Ca2+ sequestration into secretory vesicles was not inhibited by heparin (50 μg/ml), whereas Ins(1,4,5)P3 induced Ca2+ release was completely inhibited, indicating two different receptors for Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Furthermore, Ins(1,3,4,5)P4 was as effective at 4°C as at 24°C in sequestering Ca2+ into secretory vesicles, implying Ca2+ sequestration through receptor-operated Ca2+ channels or activation of the Ca2+-exchange mechanism by Ins(1,3,4,5)P4. The Ca2+-sequestering activity of Ins(1,3,4,5)P4 has also been demonstrated with 45Ca2+; 10 μM-Ins(l,3, 4,5)P4 induced rapid uptake of 45Ca2+ into secretory vesicles optimized for Ca2+ uptake, whereas 10 μM-Ins(1,4,5)P2 induced 45Ca2+ release from secretory vesicles in similar experiments.