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Article
Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone
(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an N-methyl-D-aspartate receptor...
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Article
Open AccessSignificant Functional Differences Between Dopamine D4 Receptor Polymorphic Variants Upon Heteromerization with α1A Adrenoreceptors
The functional role of the dopamine D4 receptor (D4R) and its main polymorphic variants has become more evident with the demonstration of heteromers of D4R that control the function of frontal cortico-striatal ne...
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Article
Open AccessDecreased striatal adenosine A2A-dopamine D2 receptor heteromerization in schizophrenia
According to the adenosine hypothesis of schizophrenia, the classically associated hyperdopaminergic state may be secondary to a loss of function of the adenosinergic system. Such a hypoadenosinergic state mig...
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Article
Open AccessControl of glutamate release by complexes of adenosine and cannabinoid receptors
It has been hypothesized that heteromers of adenosine A2A receptors (A2AR) and cannabinoid CB1 receptors (CB1R) localized in glutamatergic nerve terminals mediate the integration of adenosine and endocannabinoid ...
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Article
Biased G Protein-Independent Signaling of Dopamine D1-D3 Receptor Heteromers in the Nucleus Accumbens
Several studies found in vitro evidence for heteromerization of dopamine D1 receptors (D1R) and D3 receptors (D3R), and it has been postulated that functional D1R-D3R heteromers that are normally present in the v...
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Article
Revisiting the Functional Role of Dopamine D4 Receptor Gene Polymorphisms: Heteromerization-Dependent Gain of Function of the D4.7 Receptor Variant
The two most common polymorphisms of the human DRD4 gene encode a dopamine D4 receptor (D4R) with four or seven repeats of a proline-rich sequence of 16 amino acids (D4.4R or D4.7R). Although the seven-repeat pol...
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Article
Astrocytic Mechanisms Involving Kynurenic Acid Control Δ9-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas
The reinforcing effects of Δ9-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynureni...
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Article
Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron
While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfun...
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Article
α2A- and α2C-Adrenoceptors as Potential Targets for Dopamine and Dopamine Receptor Ligands
The poor norepinephrine innervation and high density of Gi/o-coupled α2A- and α2C-adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an ...
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Article
Open AccessEvidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase
G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interaction...
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Article
Open AccessGs- versus Golf-dependent functional selectivity mediated by the dopamine D1 receptor
The two highly homologous subtypes of stimulatory G proteins Gαs (Gs) and Gαolf (Golf) display contrasting expression patterns in the brain. Golf is predominant in the striatum, while Gs is predominant in the ...
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Chapter
What Is the Role of Adenosine Tone and Adenosine Receptors in Huntington’s Disease?
Huntington’s disease (HD) is a devastating hereditary neurodegenerative disorder caused by a CAG mutation within the IT15 gene encoding huntingtin protein. Even though mutant and normal huntingtin are ubiquito...
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Article
Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders
The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants able to cause substance use disorders (SUD). Caffeine produces psychomotor-activating, reinforci...
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Article
Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid
α7-nicotinic acetylcholine receptors (α7nAChRs) modulate the effects of the main psychoactive ingredient of marijuana, Δ9-tetrahydrocannabinol (THC), in the brain. Here the authors show that pharmacologically enh...
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Protocol
Detection of Receptor Heteromers Involving Dopamine Receptors by the Sequential BRET-FRET Technology
Until very recently, dopamine receptors, like other G-protein-coupled receptors, were believed to function as individual units on the cell surface. Now it has been described by several groups including ours th...
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Chapter
Role of Striatal A2A Receptor Subpopulations in Neurological Disorders
A very significant density of adenosine A2A receptors (A2AR) is present in the striatum, where they are preferentially localized postsynaptically in enkephalinergic-GABAergic-medium spiny neurons (enkephalinergic...
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Article
Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats
Adenosine receptors are involved in cocaine and methamphetamine discrimination and exposure to caffeine can affect behavioral effects of nicotine in rats.
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Article
Building a new conceptual framework for receptor heteromers
Receptor heteromers constitute a new area of research that is resha** our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that s...
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Article
Dopamine D2 and Adenosine A2A Receptors Regulate NMDA-Mediated Excitation in Accumbens Neurons Through A2A–D2 Receptor Heteromerization
Bursting activity of striatal medium spiny neurons results from membrane potential oscillations between a down- and an upstate that could be regulated by G-protein-coupled receptors. Among these, dopamine D2 and ...
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Article
Detection of heteromerization of more than two proteins by sequential BRET-FRET
Many proteins, including G protein–coupled receptors (GPCRs), interact to form oligomers at the cell surface. A combination of bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy...
