THE HUMAN MUSCARINIC M1 ACETYLCHOLINE-RECEPTOR, WHEN EXPRESSED IN CHO CELLS, ACTIVATES AND DOWN-REGULATES BOTH G(Q)ALPHA AND G(11)ALPHA EQUALLY AND NONSELECTIVELY

被引:52
作者
MULLANEY, I
MITCHELL, FM
MCCALLUM, JF
BUCKLEY, NJ
MILLIGAN, G
机构
[1] UNIV GLASGOW,DEPT BIOCHEM,MOLEC PHARMACOL GRP,GLASGOW G12 8QQ,SCOTLAND
[2] UNIV GLASGOW,DEPT PHARMACOL,GLASGOW G12 8QQ,SCOTLAND
[3] NATL INST MED RES,LONDON NW7 1AA,ENGLAND
基金
英国惠康基金;
关键词
GUANINE NUCLEOTIDE BINDING PROTEIN; PHOSPHOLIPASE-C; INOSITOL TRISPHOSPHATE; MUSCARINIC ACETYLCHOLINE RECEPTOR;
D O I
10.1016/0014-5793(93)81401-K
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
CHO cells express both of the phosphoinositidase C-linked G-proteins G(q) and G11 . G11alpha is some 2.5-fold more highly expressed than G(q)alpha in membranes of these cells. Following transfection and stable expression of CHO cells with DNA encoding the human muscarinic M1 acetylcholine (HM1) receptor, chronic treatment of the cells with the cholinergic agonist carbachol resulted in down-regulation of membrane levels of both G(q)alpha and G11alpha. Dose-response curves to carbachol produced identical EC50 values for agonist-induced down-regulation of the two G-proteins and both were down-regulated with the same time course. These data indicate that the HM1 receptor interacts with and activates both G(q)alpha and G11alpha equivalently and non-selectively in a whole cell system in which the receptor has access to both G-proteins.
引用
收藏
页码:241 / 245
页数:5
相关论文
共 19 条
[1]  
ARAGAY AM, 1992, J BIOL CHEM, V267, P24983
[2]  
BLANK JL, 1991, J BIOL CHEM, V266, P18206
[3]  
BUCKLEY NJ, 1989, MOL PHARMACOL, V35, P469
[4]   ISOZYME-SELECTIVE STIMULATION OF PHOSPHOLIPASE C-BETA-2 BY G-PROTEIN BETA-GAMMA-SUBUNITS [J].
CAMPS, M ;
CAROZZI, A ;
SCHNABEL, P ;
SCHEER, A ;
PARKER, PJ ;
GIERSCHIK, P .
NATURE, 1992, 360 (6405) :684-686
[5]   ACTIVATION OF PHOSPHATIDYLINOSITOL LIPID-SPECIFIC PHOSPHOLIPASE C-BETA-3 BY G-PROTEIN BETA-GAMMA SUBUNITS [J].
CAROZZI, A ;
CAMPS, M ;
GIERSCHIK, P ;
PARKER, PJ .
FEBS LETTERS, 1993, 315 (03) :340-342
[6]   SUBUNITS-BETA-GAMMA OF HETEROTRIMERIC G-PROTEIN ACTIVATE BETA-2 ISOFORM OF PHOSPHOLIPASE-C [J].
KATZ, A ;
WU, DQ ;
SIMON, MI .
NATURE, 1992, 360 (6405) :686-689
[7]   G-ALPHA-11 AND G-ALPHA-Q GUANININE NUCLEOTIDE REGULATORY PROTEINS DIFFERENTIALLY MODULATE THE RESPONSE TO THYROTROPIN-RELEASING-HORMONE IN XENOPUS OOCYTES [J].
LIPINSKY, D ;
GERSHENGORN, MC ;
ORON, Y .
FEBS LETTERS, 1992, 307 (02) :237-240
[8]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[9]   AGONIST CONTROL OF G-PROTEIN LEVELS [J].
MILLIGAN, G ;
GREEN, A .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1991, 12 (06) :207-209
[10]  
MILLIGAN G, 1993, IN PRESS J NEUROCHEM