 |
 Previous Article | Next Article 
The Journal of Neuroscience, November 1, 1999, 19(21):9271-9280
The CB1 Cannabinoid Receptor Can Sequester G-Proteins, Making
Them Unavailable to Couple to Other Receptors
Clemente
Vásquez and
Deborah
L.
Lewis
Department of Pharmacology and Toxicology, Medical College of
Georgia, Augusta, Georgia 30912-2300
We tested the hypothesis that human CB1 cannabinoid receptors
(hCB1) can sequester Gi/o-proteins from a common pool and
prevent other receptors from signaling. Human CB1 cannabinoid receptors were expressed in superior cervical ganglion (SCG) neurons by microinjection of hCB1 cDNA. Expression of hCB1 cannabinoid receptors abolished the Ca2+ current inhibition by endogenous
pertussis toxin-sensitive Gi/o-coupled receptors for
norepinephrine (NE) and somatostatin (SOM) but not by endogenous
pertussis toxin-insensitive Gs-coupled receptors for
vasoactive intestinal polypeptide. Signaling by NE was rescued by expression of G oB, G 1,
and G 3. Expression of mGluR2 metabotropic glutamate
receptors, another pertussis toxin-sensitive G-protein-coupled receptor, had no effect on the signaling by NE or SOM. Some hCB1 receptors were constitutively active because the cannabinoid receptor inverse agonist SR 141617A enhanced the Ca2+
current. Some hCB1 receptors also appear to be precoupled to Gi/o-proteins because the cannabinoid agonist WIN 55,212-2
decreased the Ca2+ current at a time when no
G-proteins were available to couple to 2-adrenergic and
somatostatin receptors. In SCG neurons microinjected with a lower
concentration of hCB1 cDNA, the effect of SR 141716A was reduced, and
the response to NE and SOM was partially restored. Subsequent to the
application of SR 141716A, the Ca2+ current
inhibition by NE and SOM was abolished. These results suggest that both
the active and inactive states of the hCB1 receptor can sequester
Gi/o-proteins from a common pool. Cannabinoid receptors thus have the potential to prevent other Gi/o-coupled
receptors from transducing their biological signals.
Key words:
calcium channels; G-proteins; cannabinoid receptor; G-protein-coupled receptors; patch clamp; ion channels; CB1; constitutively active receptors
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219271-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
Z. Helyes, E. Pinter, K. Sandor, K. Elekes, A. Banvolgyi, D. Keszthelyi, E. Szoke, D. M. Toth, Z. Sandor, L. Kereskai, et al.
Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice
PNAS,
August 4, 2009;
106(31):
13088 - 13093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. Khasabova, S. G. Khasabov, C. Harding-Rose, L. G. Coicou, B. A. Seybold, A. E. Lindberg, C. D. Steevens, D. A. Simone, and V. S. Seybold
A Decrease in Anandamide Signaling Contributes to the Maintenance of Cutaneous Mechanical Hyperalgesia in a Model of Bone Cancer Pain
J. Neurosci.,
October 29, 2008;
28(44):
11141 - 11152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Anavi-Goffer, D. Fleischer, D. P. Hurst, D. L. Lynch, J. Barnett-Norris, S. Shi, D. L. Lewis, S. Mukhopadhyay, A. C. Howlett, P. H. Reggio, et al.
Helix 8 Leu in the CB1 Cannabinoid Receptor Contributes to Selective Signal Transduction Mechanisms
J. Biol. Chem.,
August 24, 2007;
282(34):
25100 - 25113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Turu, A. Simon, P. Gyombolai, L. Szidonya, G. Bagdy, Z. Lenkei, and L. Hunyady
The Role of Diacylglycerol Lipase in Constitutive and Angiotensin AT1 Receptor-stimulated Cannabinoid CB1 Receptor Activity
J. Biol. Chem.,
March 16, 2007;
282(11):
7753 - 7757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Margas, I. Zubkoff, H. G. Schuler, P. K. Janicki, and V. Ruiz-Velasco
Modulation of Ca2+ Channels by Heterologously Expressed Wild-Type and Mutant Human {micro}-Opioid Receptors (hMORs) Containing the A118G Single-Nucleotide Polymorphism
J Neurophysiol,
February 1, 2007;
97(2):
1058 - 1067.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chen, A. Neu, A. L. Howard, C. Foldy, J. Echegoyen, L. Hilgenberg, M. Smith, K. Mackie, and I. Soltesz
Prevention of Plasticity of Endocannabinoid Signaling Inhibits Persistent Limbic Hyperexcitability Caused by Developmental Seizures
J. Neurosci.,
January 3, 2007;
27(1):
46 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Neu, C. Foldy, and I. Soltesz
Postsynaptic origin of CB1-dependent tonic inhibition of GABA release at cholecystokinin-positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus
J. Physiol.,
January 1, 2007;
578(1):
233 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Andressen, J. H. Norum, F. O. Levy, and K. A. Krobert
Activation of Adenylyl Cyclase by Endogenous Gs-Coupled Receptors in Human Embryonic Kidney 293 Cells Is Attenuated by 5-HT7 Receptor Expression
Mol. Pharmacol.,
January 1, 2006;
69(1):
207 - 215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mukhopadhyay and A. C. Howlett
Chemically Distinct Ligands Promote Differential CB1 Cannabinoid Receptor-Gi Protein Interactions
Mol. Pharmacol.,
June 1, 2005;
67(6):
2016 - 2024.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Bayatti, H. Hermann, B. Lutz, and C. Behl
Corticotropin-Releasing Hormone-Mediated Induction of Intracellular Signaling Pathways and Brain-Derived Neurotrophic Factor Expression Is Inhibited by the Activation of the Endocannabinoid System
Endocrinology,
March 1, 2005;
146(3):
1205 - 1213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. L. McLemore, R. Z. B. Cooper, K. A. Richardson, A. V. Mason, C. Marshall, F. J. Northington, and E. B. Gauda
Cannabinoid receptor expression in peripheral arterial chemoreceptors during postnatal development
J Appl Physiol,
October 1, 2004;
97(4):
1486 - 1495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hirasawa, Y. Schwab, S. Natah, C. J. Hillard, K. Mackie, K. A. Sharkey, and Q. J. Pittman
Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain
J. Physiol.,
September 1, 2004;
559(2):
611 - 624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Guo and S. R. Ikeda
Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 Cannabinoid Receptors Heterologously Expressed in Mammalian Neurons
Mol. Pharmacol.,
March 1, 2004;
65(3):
665 - 674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Jarrahian, V. J. Watts, and E. L. Barker
D2 Dopamine Receptors Modulate G{alpha}-Subunit Coupling of the CB1 Cannabinoid Receptor
J. Pharmacol. Exp. Ther.,
March 1, 2004;
308(3):
880 - 886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. G. Reich, S. E. Mason, and B. E. Alger
Novel Form of LTD Induced by Transient, Partial Inhibition of the Na,K-Pump in Rat Hippocampal CA1 Cells
J Neurophysiol,
January 1, 2004;
91(1):
239 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Solinas, L. V. Panlilio, K. Antoniou, L. A. Pappas, and S. R. Goldberg
The Cannabinoid CB1 Antagonist N-Piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide (SR-141716A) Differentially Alters the Reinforcing Effects of Heroin under Continuous Reinforcement, Fixed Ratio, and Progressive Ratio Schedules of Drug Self-Administration in Rats
J. Pharmacol. Exp. Ther.,
July 1, 2003;
306(1):
93 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ruiu, G. A. Pinna, G. Marchese, J.-M. Mussinu, P. Saba, S. Tambaro, P. Casti, R. Vargiu, and L. Pani
Synthesis and Characterization of NESS 0327: A Novel Putative Antagonist of the CB1 Cannabinoid Receptor
J. Pharmacol. Exp. Ther.,
July 1, 2003;
306(1):
363 - 370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Hurst, D. L. Lynch, J. Barnett-Norris, S. M. Hyatt, H. H. Seltzman, M. Zhong, Z.-H. Song, J. Nie, D. Lewis, and P. H. Reggio
N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A) Interaction with LYS 3.28(192) Is Crucial for Its Inverse Agonism at the Cannabinoid CB1 Receptor
Mol. Pharmacol.,
December 1, 2002;
62(6):
1274 - 1287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Nie and D. L. Lewis
Structural Domains of the CB1 Cannabinoid Receptor That Contribute to Constitutive Activity and G-Protein Sequestration
J. Neurosci.,
November 15, 2001;
21(22):
8758 - 8764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Huestis, D. A. Gorelick, S. J. Heishman, K. L. Preston, R. A. Nelson, E. T. Moolchan, and R. A. Frank
Blockade of Effects of Smoked Marijuana by the CB1-Selective Cannabinoid Receptor Antagonist SR141716
Arch Gen Psychiatry,
April 1, 2001;
58(4):
322 - 328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Martin and P. L. Prather
Interaction of Co-Expressed {micro}- and {delta}-Opioid Receptors in Transfected Rat Pituitary GH3 Cells
Mol. Pharmacol.,
April 1, 2001;
59(4):
774 - 783.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Dosil, K. A. Schandel, E. Gupta, D. D. Jenness, and J. B. Konopka
The C Terminus of the Saccharomyces cerevisiae alpha -Factor Receptor Contributes to the Formation of Preactivation Complexes with Its Cognate G Protein
Mol. Cell. Biol.,
July 15, 2000;
20(14):
5321 - 5329.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. P. Meschler, F. A. Clarkson, P. J. Mathews, A. C. Howlett, and B. K. Madras
D2, but Not D1 Dopamine Receptor Agonists Potentiate Cannabinoid-Induced Sedation in Nonhuman Primates
J. Pharmacol. Exp. Ther.,
March 1, 2000;
292(3):
952 - 959.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. Varma, G. C. Carlson, C. Ledent, and B. E. Alger
Metabotropic Glutamate Receptors Drive the Endocannabinoid System in Hippocampus
J. Neurosci.,
December 15, 2001;
21(24):
RC188 - RC188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
