Activation of type II adenylate cyclase by D-2 and D-4 but not D-3 dopamine receptors

被引:54
作者
Watts, VJ [1 ]
Neve, KA [1 ]
机构
[1] OREGON HLTH SCI UNIV,DEPT BEHAV NEUROSCI,PORTLAND,OR 97201
关键词
D O I
10.1124/mol.52.2.181
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The D-2-like dopamine receptors couple to a variety of signal transduction pathways, including inhibition of adenylate cyclase, mitogenesis, and activation of potassium channels. Although these effects are mediated via pertussis toxin-sensitive G proteins, G(i/o), it is likely that some of these effects are influenced by the release of G protein beta gamma subunits. Type II adenylate cyclase (ACII) is highly regulated by multiple biochemical stimuli, including protein kinase C, forskolin, G protein alpha subunits, and G protein beta gamma subunits. The ability of beta gamma subunits to activate this enzyme In the presence of activated alpha(s) has been particularly well characterized. Although stimulation by beta gamma subunits has been described as conditional on the presence of activated alpha(s), beta gamma subunits also potentiate ACII activity after activation of protein kinase C. We created stable cell lines expressing ACII and the D-2L receptor, the D-3 receptor, or the D-4.4 receptor. Activation of D-2L or D-4.4 receptors, but not D-3 receptors, potentiated beta-adrenergic receptor/G(s)-stimulated activity of ACII, as measured by the intracellular accumulation of cAMP. Similarly, stimulation of D-2L or D-4.4 receptors potentiated phorbol ester-stimulated ACII activity in the absence of activated alpha(s), whereas stimulation of D-3 receptors did not. The effect of D-2-like receptor stimulation was blocked by pretreatment with pertussis toxin and by inhibition of protein kinase C. We propose that activation of both D-2L and D-4.4 dopamine receptors potentiated phorbol-12-myristate-13-acetate-stimulated ACII activity through the release of beta gamma subunits from pertussis toxin-sensitive G proteins. In contrast, the lack of D-3 receptor-mediated effects suggests that stimulation of D-3 receptors does not result in an appreciable release of beta gamma subunits.
引用
收藏
页码:181 / 186
页数:6
相关论文
共 31 条
[1]   MODULATION OF INTRACELLULAR CYCLIC-AMP LEVELS BY DIFFERENT HUMAN DOPAMINE D4 RECEPTOR VARIANTS [J].
ASGHARI, V ;
SANYAL, S ;
BUCHWALDT, S ;
PATERSON, A ;
JOVANOVIC, V ;
VANTOL, HHM .
JOURNAL OF NEUROCHEMISTRY, 1995, 65 (03) :1157-1165
[2]  
CHAN JSC, 1995, J NEUROCHEM, V65, P2682
[3]  
CHIO CL, 1994, MOL PHARMACOL, V45, P51
[4]  
CHOI EJ, 1992, J BIOL CHEM, V267, P12440
[5]   REGULATION AND FUNCTIONAL-CHARACTERIZATION OF A RAT RECOMBINANT DOPAMINE D3 RECEPTOR [J].
COX, BA ;
ROSSER, MP ;
KOZLOWSKI, MR ;
DUWE, KM ;
NEVE, RL ;
NEVE, KA .
SYNAPSE, 1995, 21 (01) :1-9
[6]   HORMONAL-STIMULATION OF ADENYLYL CYCLASE THROUGH GI-PROTEIN BETA-GAMMA-SUBUNITS [J].
FEDERMAN, AD ;
CONKLIN, BR ;
SCHRADER, KA ;
REED, RR ;
BOURNE, HR .
NATURE, 1992, 356 (6365) :159-161
[7]   FUNCTIONALLY ACTIVE TARGETING DOMAIN OF THE BETA-ADRENERGIC-RECEPTOR KINASE - AN INHIBITOR OF G-BETA-GAMMA-MEDIATED STIMULATION OF TYPE-II ADENYLYL-CYCLASE [J].
INGLESE, J ;
LUTTRELL, LM ;
INIGUEZLLUHI, JA ;
TOUHARA, K ;
KOCH, WJ ;
LEFKOWITZ, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :3637-3641
[8]   PHORBOL ESTER-INDUCED STIMULATION AND PHOSPHORYLATION OF ADENYLYL-CYCLASE-2 [J].
JACOBOWITZ, O ;
IYENGAR, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (22) :10630-10634
[9]  
KANTERMAN RY, 1991, MOL PHARMACOL, V39, P364
[10]  
LUSTIG KD, 1993, J BIOL CHEM, V268, P13900