A RAPID ATTENUATION OF MUSCARINIC AGONIST-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS PRECEDES RECEPTOR SEQUESTRATION IN HUMAN SH-SY-5Y NEUROBLASTOMA-CELLS

被引:23
作者
FISHER, SK [1 ]
SLOWIEJKO, DM [1 ]
MCEWEN, EL [1 ]
机构
[1] UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48104
关键词
MUSCARINIC CHOLINERGIC RECEPTOR; PHOSPHOINOSITIDE HYDROLYSIS; INOSITOL 1,4,5-TRISPHOSPHATE; SH-SY-5Y NEUROBLASTOMA; DESENSITIZATION;
D O I
10.1007/BF00971329
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Agonist occupancy of muscarinic cholinergic receptors in human SH-SY-5Y neuroblastoma cells elicited two kinetically distinct phases of phosphoinositide hydrolysis when monitored by either an increased mass of inositol 1,4,5-trisphosphate, or the accumulation of a total inositol phosphate fraction. Within 5s of the addition of the muscarinic agonist, oxotremorine-M, the phosphoinositide pool was hydrolyzed at a maximal rate of 9.5%/min. This initial phase of phosphoinositide hydrolysis was short-lived (t(1/2) = 14s) and after 60s of agonist exposure, the rate of inositol lipid breakdown had declined to a steady stare level of 3.4%/min which was then maintained for at least 5-10 min. This rapid, but partial, attenuation of muscarinic receptor stimulated phosphoinositide hydrolysis occurred prior to the agonist-induced internalization of muscarinic receptors.
引用
收藏
页码:549 / 554
页数:6
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