 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, March 1, 1999, 19(5):1698-1707
Activation of Human D3 Dopamine Receptor Inhibits P/Q-Type Calcium Channels and Secretory Activity in AtT-20 Cells
Eldo V. Kuzhikandathil and Gerry S. Oxford Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
The D3 dopamine receptor is postulated to play an important role in the regulation of neurotransmitter secretion at both pre- and postsynaptic terminals. However, this hypothesis and the underlying mechanisms remain untested because of the lack of D3-selective ligands, paucity of appropriate model secretory systems, and the weak and inconsistent coupling of D3 receptors to classical signal transduction pathways. The absence of ligands that selectively discriminate between D3 and D2 receptors in vivo precludes the study of D3 receptor function in the brain and necessitates the use of heterologous expression systems. In this report we demonstrate that activation of the human D3 dopamine receptor expressed in the AtT-20 neuroendocrine cell line causes robust inhibition of P/Q-type calcium channels via pertussis toxin-sensitive G-proteins. In addition, using the vesicle trafficking dye FM1-43, we show that D3 receptor activation significantly inhibits spontaneous secretory activity in these cells. Our results not only support the hypothesis that the D3 receptor can regulate secretory activity but also provide insight into the underlying signaling mechanisms. We propose a functional model in which the D3 receptor tightly regulates neurotransmitter release at a synapse by only allowing the propagation of spikes above a certain frequency or burst-duration threshold.
Key words: D3 dopamine receptor; calcium channels; secretion; FM1-43; AtT-20 cells; high-pass filter
Copyright © 1999 Society for Neuroscience 0270-6474/99/1951698-10$05.00/0
This article has been cited by other articles:
S. R. Vorel, C. R. Ashby Jr, M. Paul, X. Liu, R. Hayes, J. J. Hagan, D. N. Middlemiss, G. Stemp, and E. L. Gardner
Dopamine D3 Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats
J. Neurosci., November 1, 2002; 22(21): 9595 - 9603.
[Abstract] [Full Text] [PDF]
E. V. Kuzhikandathil and G. S. Oxford
Classic D1 Dopamine Receptor Antagonist R-(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) Directly Inhibits G Protein-Coupled Inwardly Rectifying Potassium Channels
Mol. Pharmacol., July 1, 2002; 62(1): 119 - 126.
[Abstract] [Full Text] [PDF]
B. T. Chen, M. V. Avshalumov, and M. E. Rice
H2O2 Is a Novel, Endogenous Modulator of Synaptic Dopamine Release
J Neurophysiol, June 1, 2001; 85(6): 2468 - 2476.
[Abstract] [Full Text] [PDF]
S. Jones, J. L. Kornblum, and J. A. Kauer
Amphetamine Blocks Long-Term Synaptic Depression in the Ventral Tegmental Area
J. Neurosci., August 1, 2000; 20(15): 5575 - 5580.
[Abstract] [Full Text] [PDF]
M. J. Millan, A. Gobert, A. Newman-Tancredi, F. Lejeune, D. Cussac, J.-M. Rivet, V. Audinot, T. Dubuffet, and G. Lavielle
S33084, a Novel, Potent, Selective, and Competitive Antagonist at Dopamine D3-Receptors: I. Receptorial, Electrophysiological and Neurochemical Profile Compared with GR218,231 and L741,626
J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 1048 - 1062.
[Abstract] [Full Text]
K.-M. Kim, K. J. Valenzano, S. R. Robinson, W. D. Yao, L. S. Barak, and M. G. Caron
Differential Regulation of the Dopamine D2 and D3 Receptors by G Protein-coupled Receptor Kinases and beta -Arrestins
J. Biol. Chem., September 28, 2001; 276(40): 37409 - 37414.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|