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D3 dopamine receptor activates phospholipase D through a pertussis toxin-insensitive pathway
P Benjamin Everett1, Susan E Senogles
1Department of Molecular Sciences, University of Tennessee Health Science Center, Suite G01, 858 Madison Avenue, Memphis, TN 38163, USA.
Neuroscience Letters
|October 27, 2004
Summary
The D3 dopamine receptor activates phospholipase D (PLD) signaling, a novel pathway independent of Gi/o proteins. This discovery expands our understanding of D3 receptor function beyond its known PTX-sensitive mechanisms.
Area of Science:
- Neuropharmacology
- Molecular Biology
- Cell Signaling
Background:
- The D3 dopamine receptor's signaling pathways are not fully understood.
- Known D3 receptor functions involve PTX-sensitive G-proteins, inhibiting adenylyl cyclase and regulating ion channels.
Purpose of the Study:
- To investigate novel signaling pathways activated by the D3 dopamine receptor.
- To determine if D3 receptor activation of phospholipase D (PLD) involves PTX-sensitive G-proteins.
Main Methods:
- HEK 293 cells expressing the human D3 receptor were used.
- Agonist-induced PLD activity was measured.
- The effects of D3-specific antagonists and PTX pretreatment were assessed.
Main Results:
- D3 receptor activation led to a dose-dependent increase in PLD activity.
- D3-specific antagonists blocked agonist-induced PLD activation.
- Pertussis toxin (PTX) pretreatment did not affect D3 receptor-mediated PLD activation.
Conclusions:
- The D3 dopamine receptor activates phospholipase D (PLD) in a novel signaling pathway.
- This D3 receptor-mediated PLD activation is independent of Gi/o G-proteins.
- This represents the first identified effector system for D3 receptors signaling without Gi/o intermediates.