![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Medical Research Service, Veterans Affairs Medical Center and
Department of Behavioral Neuroscience, Oregon Health Sciences
University, Portland, Oregon 97201
The D2-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, Gi/o, it is likely that some of these effects are
influenced by the release of G protein 
subunits. Type II
adenylate cyclase (ACII) is highly regulated by multiple biochemical
stimuli, including protein kinase C, forskolin, G protein 
subunits,
and G protein subunits. The ability of subunits to
activate this enzyme in the presence of activated s has
been particularly well characterized. Although stimulation by
subunits has been described as conditional on the presence of activated
s, subunits also potentiate ACII activity after
activation of protein kinase C. We created stable cell lines expressing
ACII and the D2L receptor, the D3 receptor, or
the D4.4 receptor. Activation of D2L or
D4.4 receptors, but not D3 receptors,
potentiated -adrenergic receptor/Gs-stimulated activity
of ACII, as measured by the intracellular accumulation of cAMP.
Similarly, stimulation of D2L or D4.4 receptors
potentiated phorbol ester-stimulated ACII activity in the absence of
activated s, whereas stimulation of D3
receptors did not. The effect of D2-like receptor
stimulation was blocked by pretreatment with pertussis toxin and by
inhibition of protein kinase C. We propose that activation of both
D2L and D4.4 dopamine receptors potentiated phorbol-12-myristate-13-acetate-stimulated ACII activity through the
release of subunits from pertussis toxin-sensitive G proteins. In contrast, the lack of D3 receptor-mediated effects
suggests that stimulation of D3 receptors does not result
in an appreciable release of subunits.
This article has been cited by other articles:
|
|
 |
|
  C. H. Nguyen and V. J. Watts Dexamethasone-Induced Ras Protein 1 Negatively Regulates Protein Kinase C {delta}: Implications for Adenylyl Cyclase 2 Signaling Mol. Pharmacol., May 1, 2006; 69(5): 1763 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wu and J. J. Hablitz Cooperative Activation of D1 and D2 Dopamine Receptors Enhances a Hyperpolarization-Activated Inward Current in Layer I Interneurons J. Neurosci., July 6, 2005; 25(27): 6322 - 6328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Vortherms and V. J. Watts Sensitization of Neuronal A2A Adenosine Receptors after Persistent D2 Dopamine Receptor Activation J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 221 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yao, P. Fan, Z. Jiang, W. S. Mailliard, A. S. Gordon, and I. Diamond Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-{beta}{gamma} dimers PNAS, November 25, 2003; 100(24): 14379 - 14384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. W. Hopf, M. G. Cascini, A. S. Gordon, I. Diamond, and A. Bonci Cooperative Activation of Dopamine D1 and D2 Receptors Increases Spike Firing of Nucleus Accumbens Neurons via G-Protein {beta}{gamma} Subunits J. Neurosci., June 15, 2003; 23(12): 5079 - 5087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Cumbay and V. J. Watts Heterologous Sensitization of Recombinant Adenylate Cyclases by Activation of D2 Dopamine Receptors J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 1201 - 1209. [Abstract] [Full Text]
|
|
|
|
|
|
D. Cussac, A. Newman-Tancredi, V. Pasteau, and M. J. Millan Human Dopamine D3 Receptors Mediate Mitogen-Activated Protein Kinase Activation Via a Phosphatidylinositol 3-Kinase and an Atypical Protein Kinase C-Dependent Mechanism Mol. Pharmacol., November 1, 1999; 56(5): 1025 - 1030. [Abstract] [Full Text]
|
|
|
|
|
|
J. F. M. Vanhauwe, N. Fraeyman, B. J. B. Francken, W. H. M. L. Luyten, and J. E. Leysen Comparison of the Ligand Binding and Signaling Properties of Human Dopamine D2 and D3 Receptors in Chinese Hamster Ovary Cells J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 908 - 916. [Abstract] [Full Text]
|
|
|
|
|
|
A. Newman-Tancredi, D. Cussac, V. Audinot, V. Pasteau, S. Gavaudan, and M. J. Millan G Protein Activation by Human Dopamine D3 Receptors in High-Expressing Chinese Hamster Ovary Cells: A Guanosine-5'-O-(3-[35S]thio)-Triphosphate Binding and Antibody Study Mol. Pharmacol., March 1, 1999; 55(3): 564 - 574. [Abstract] [Full Text]
|
|
|
|
|
|
V. J. Watts, B. L. Wiens, M. G. Cumbay, M. N. Vu, R. L. Neve, and K. A. Neve Selective Activation of Galpha o by D2L Dopamine Receptors in NS20Y Neuroblastoma Cells J. Neurosci., November 1, 1998; 18(21): 8692 - 8699. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
