2-Hydroxyethyl α-D-glucopyranoside 2,3′,4′-trisphosphate: a novel metabolically resistant adenophostin A and myo-inositol 1,4,5-trisphosphate analogue potently interacts with the myo-inositol 1,4,5-trispbosphate receptor

Abstract

420s Biochemical Soclety Transactlons ( 1 995) 23 2-Hydroxyethyl a-D-glucopyranoside 2,3',4'-trisphosphate: a novel metabolieally resistant adenophostin A and myo-inositol 1,4,5-trispbosphate analogue potently interacts with tbe myoioositol 1,4,5-trispbospbate receptor.

Effects of Adenophostin-A and Inositol-1,4,5-trisphosphate on Cl−Currents inXenopus laevisOocytes

“…It has been proposed that the 3-and 4-phosphates on the glucose ring of adenophostin-A assume the same role as the 4-and 5-phosphates in IP 3 (10). Consistent with this idea is the finding that 2-hydroxyethyl-␣-D-glucopyranoside-2,3Ј,4Ј-trisphosphate is also capable of binding to the IP 3 receptor and releasing Ca 2ϩ from internal stores, although with ϳ1000-fold lower potency than adenophostin-A (11). Although the effects of adenophostin-A on Ca 2ϩ release have been demonstrated in microsomal preparations (10), permeabilized cells (10), and purified reconstituted IP 3 receptors (12), the effects of adenophostin-A in intact cells have not been investigated.…”

Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle

“…The most critical structural feature of InsP 3 is its vicinal D-4,5-bisphosphate motif, with the 5-phosphate being the dominant partner in receptor interaction (Wilcox et al, 1997). The 1-phosphate also contributes to the receptor interaction specificity (Nahorski and Potter, 1989), potency (Willcocks et al, 1989;Jenkinson et al, 1992), and efficacy (Wilcox et al, 1995(Wilcox et al, , 1997. The hydroxyl group in 6-position appears to make a major contribution to the binding interactions with the receptor (Safrany et al, 1991), whereas FIG.…”

“…The third phosphate of adenophostins (2Ј-phos-490 phate) is essential for high potency (Shuto et al, 1998); its removal causes a 1000-fold decrease in binding affinity in rat cerebellar microsomes (Takahashi et al, 1994) and a 2000-fold lower affinity to purified rat cerebellar InsP 3 R (Takahashi et al, 1993). The adenosine component at the 1Љ-position of the glucopyranose ring is also necessary for the high potency of adenophostins (Wilcox et al, 1995;Murphy et al, 1997;Shuto et al, 1998;de Kort et al, 2000).…”

“…Adenophostins possess important structural features for agonism at the InsP 3 R. The 4-and 3-positions of the glucose 3,4-bisphosphate moiety and the 2-position hydroxyl group were shown by molecular modeling to be similar to 4-, 5-, and 6-positions, respectively, of InsP 3 (Takahashi et al, 1994;Wilcox et al, 1995), and both structural features are as essential for Ca 2ϩ -releasing activity in rabbit permeabilized platelets (Murphy et al, 1997). The third phosphate of adenophostins (2Ј-phos-490 phate) is essential for high potency (Shuto et al, 1998); its removal causes a 1000-fold decrease in binding affinity in rat cerebellar microsomes (Takahashi et al, 1994) and a 2000-fold lower affinity to purified rat cerebellar InsP 3 R (Takahashi et al, 1993).…”

Structure and Function of Inositol 1,4,5-Trisphosphate Receptor.

“…However, its usefulness as a pharmacological tool for studies on intact cells is hampered because it may also inhibit the formation of IP3 and activate the ryanodine receptor (75). Adenophostin A and B are newly discover ed, potent and metabolically resistant agonists of IP3 receptors (76,77). In spite of structural differences from IP3, adenophostins activate Ca 2+ release channels with a potency 10 to 100-fold greater than IP3i and their actions are completely blocked by heparin.…”