THE NOVEL INS(1,4,5)P-3 ANALOG 3-AMINO-3-DEOXY-INS(1,4,5)P-3 - A PH-DEPENDENT INS(1,4,5)P-3 RECEPTOR PARTIAL AGONIST IN SH-SY5Y NEUROBLASTOMA-CELLS

被引：14

作者：

KOZIKOWSKI, AP ^{[1
]}

FAUQ, AH ^{[1
]}

WILCOX, RA ^{[1
]}

CHALLISS, RAJ ^{[1
]}

NAHORSKI, SR ^{[1
]}

机构：

[1] UNIV LEICESTER,DEPT CELL PHYSIOL & PHARMACOL,LEICESTER LE1 9HN,ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 06期

基金：

英国惠康基金;

关键词：

D O I：

10.1021/jm00032a022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have synthesized the first amino-substituted inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] analogue, D-3-amino-3-deoxy-myo-Ins(1,4,5)P3 (9). Although 9 is a full agonist at the Ca2+ mobilizing Ins(1,4,5)P3 receptor at pH 7.2 and 7.6, it is apparently a high intrinsic activity partial agonist at pH 6.8, releasing only 80% of the Ins(1,4,5)P3-sensitive Ca2+ stores of SH-SY5Y cells. Additionally, 9 was able to fully displace [H-3]Ins(1,4,5)P3 from binding sites in rat cerebellum membranes at both pH 6.8 and 7.6, indicating a full interaction with the Ins(1,4,5)P3 receptor. The activity displayed by this amino analogue is unexpected and may be indicative of a pH-dependent conformational change in the amino acid residues comprising the Ins(1,4,5)P3 binding site.

引用

页码：868 / 872

页数：5

共 14 条

[11] 3-POSITION MODIFICATION OF MYOINOSITOL 1,4,5-TRISPHOSPHATE - CONSEQUENCES FOR INTRACELLULAR CA2+ MOBILIZATION AND ENZYME RECOGNITION [J].

SAFRANY, ST ;

WILCOX, RA ;

LIU, CS ;

POTTER, BVL ;

NAHORSKI, SR .

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1992, 226 (03) :265-272

[12]

Shears Stephen B., 1992, Advances in Second Messenger and Phosphoprotein Research, V26, P63

[13] STEREOSELECTIVITY OF INS(1,3,4,5)P(4) RECOGNITION SITES - IMPLICATIONS FOR THE MECHANISM OF THE INS(1,3,4,5)P(4)-INDUCED CA2+ MOBILIZATION [J].

WILCOX, RA ;

CHALLISS, RAJ ;

BAUDIN, G ;

VASELLA, A ;

POTTER, BVL ;

NAHORSKI, SR .

BIOCHEMICAL JOURNAL, 1993, 294 :191-194

[14] THE ROLE OF THE 2-HYDROXYL AND 3-HYDROXYL GROUPS OF 1D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE IN THE MOBILIZATION OF CALCIUM FROM PERMEABILIZED HUMAN 1321N1 ASTROCYTOMA-CELLS [J].

WILCOX, RA ;

NAHORSKI, SR ;

SAWYER, DA ;

LIU, CS ;

POTTER, BVL .

CARBOHYDRATE RESEARCH, 1992, 234 :237-246

← 1 2 →