PHOSPHORYLATION BY CYCLIC AMP-DEPENDENT PROTEIN-KINASE MODULATES AGONIST BINDING TO THE D2-DOPAMINE RECEPTOR

被引:24
作者
ELAZAR, Z [1 ]
FUCHS, S [1 ]
机构
[1] WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL
关键词
CYCLIC AMP-DEPENDENT PROTEIN KINASE; D2-DOPAMINE RECEPTOR; PHOSPHORYLATION;
D O I
10.1111/j.1471-4159.1991.tb02564.x
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
Phosphorylation of striatal membranes by cyclic AMP-dependent protein kinase resulted in a reduction in the affinity of the D2 dopamine receptor toward its agonist N-propylnorapomorphine while the affinity to D2-specific antagonists remained unchanged. The inhibitory effects observed by phosphorylation and guanine nucleotides on agonists binding to the D2 receptor were additive. The purified D2 dopamine receptor from bovine striatum was specifically phosphorylated by cyclic AMP-dependent protein kinase with an apparent stoichiometry of 0.7 mol phosphate/mol receptor. The phosphorylated purified D2 receptor also exhibited a reduced agonist binding activity with no change in antagonist binding. The action of cyclic AMP-dependent protein kinase on both the membrane preparation and the purified D2 receptor was inhibited by a specific inhibitor of the kinase. These data indicate that phosphorylation mediated by cyclic AMP-dependent protein kinase may represent a physiological pathway for modulation of the receptor binding activity.
引用
收藏
页码:75 / 80
页数:6
相关论文
共 30 条
[11]  
ENJALBERT A, 1983, MOL PHARMACOL, V23, P576
[12]  
ENJALBERT A, 1986, J BIOL CHEM, V261, P4071
[13]   THE EFFECT OF CHOLERA-TOXIN ON THE INHIBITION OF VASOPRESSIN-STIMULATED INOSITOL PHOSPHOLIPID HYDROLYSIS IS A CYCLIC AMP-MEDIATED EVENT AT THE LEVEL OF RECEPTOR-BINDING [J].
GARDNER, SD ;
MILLIGAN, G ;
RICE, JE ;
WAKELAM, MJO .
BIOCHEMICAL JOURNAL, 1989, 259 (03) :679-684
[14]  
HOURNOT L, 1987, J BIOL CHEM, V262, P15106
[15]   REGULATION OF RECEPTOR FUNCTION BY PROTEIN-PHOSPHORYLATION [J].
HUGANIR, RL ;
GREENGARD, P .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1987, 8 (12) :472-477
[16]   ANTIBODIES AGAINST HALOPERIDOL SPECIFIC TO THE BUTYROPHENONE MOIETY [J].
KANETY, H ;
SCHREIBER, M ;
ELAZAR, Z ;
FUCHS, S .
JOURNAL OF NEUROIMMUNOLOGY, 1988, 18 (01) :25-36
[17]   A SELECTIVE EFFECT OF PROTEIN-KINASE-C ACTIVATION ON PIRENZEPINE HIGH-AFFINITY MUSCARINIC RECEPTORS IN A NEURONAL CLONE [J].
LAI, WS ;
ELFAKAHANY, EE .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1986, 129 (1-2) :201-202
[18]  
LEVITAN ES, 1988, J NEUROSCI, V8, P1152
[19]  
OHARA K, 1988, MOL PHARMACOL, V33, P290
[20]  
PAUPARDINTRITSCH D, 1985, J NEUROSCI, V5, P2522