The olfactory Olfr-78/51E2 receptor interacts with the adenosine A receptor. Effect of menthol and 1,8-cineole on A receptor-mediated signaling.

Heteromer formation is unknown for the olfactory family of G protein-coupled receptors (GPCRs). We here identified, in a heterologous system, heteromers formed by the adenosine A receptor (AR), which is a target for neuroprotection, and an olfactory receptor. AR interacts with the receptor family 51, subfamily E, member 2 (OR51E2), the human ortholog of the mouse Olfr-78, whose mRNA is differentially expressed in activated microglia treated with adenosine receptor ligands.

Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes.

The composition of the aqueous humor of patients with type 2 diabetes is relevant to understanding the underlying causes of eye-related comorbidities. Information on the composition of aqueous humor in healthy subjects is limited due to the lack of adequate controls. To carry out a metabolomics study, 31 samples of aqueous humor from healthy subjects without ocular pathology, submitted to refractive surgery and seven samples from patients with type 2 diabetes without signs of ocular pathology related to diabetes were used.

The adenosine A receptor is a therapeutic target in neurological, heart and oncogenic diseases.

Introduction: Following approval of antagonists in Parkinson's disease therapy, the A adenosine receptor (AR) is gaining interest as a target to combat a variety of diseases.

Areas Covered: This review focuses on the therapeutic potential of targeting AR inside but also outside the central nervous system, more precisely to combat cardiac arrhythmias and to boost immune-based cancer therapies. The mechanism of regulation of the immune system by adenosine (Ado) is complex since several actors are involved, namely the enzymes that produce and degrade the compound and the four Ado receptors.

Regulation of Expression of Cannabinoid CB and Serotonin 5HT Receptor Complexes by Cannabinoids in Animal Models of Hypoxia and in Oxygen/Glucose-Deprived Neurons.

Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB and serotonin 5HT receptors included. These two receptors may interact to form heteromers (CB-5HT-Hets) that are also a target of CBD.

Targeted Metabolomics Shows That the Level of Glutamine, Kynurenine, Acyl-Carnitines and Lysophosphatidylcholines Is Significantly Increased in the Aqueous Humor of Glaucoma Patients.

The composition of the aqueous humor of patients with glaucoma is relevant to understand the underlying causes of the pathology. Information on the concentration of metabolites and small molecules in the aqueous humor of healthy subjects is limited. Among the causes of the limitations is the lack of healthy controls since, until recently, they were not surgically intervened; therefore, the aqueous humor of patients operated for cataract was used as a reference.

Expression of the Adenosine A-A Receptor Heteromer in Different Brain Regions and Marked Upregulation in the Microglia of the Transgenic APP Alzheimer's Disease Model.

Adenosine (Ado) receptors have been instrumental in the detection of heteromers and other higher-order receptor structures, mainly via interactions with other cell surface G-protein-coupled receptors. Apart from the first report of the A Ado receptor interacting with the A Ado receptor, there has been more recent data on the possibility that every Ado receptor type, A, A, A, and A, may interact with each other. The aim of this paper was to look for the expression and function of the A/A receptor heteromer (AAHet) in neurons and microglia.

Ghrelin and Cannabinoid Functional Interactions Mediated by Ghrelin/CB Receptor Heteromers That Are Upregulated in the Striatum From Offspring of Mice Under a High-Fat Diet.

There is evidence of ghrelinergic-cannabinoidergic interactions in the central nervous system (CNS) that may impact on the plasticity of reward circuits. The aim of this article was to look for molecular and/or functional interactions between cannabinoid CB and ghrelin GHS-R1a receptors. In a heterologous system and using the bioluminescence resonance energy transfer technique we show that human versions of cannabinoid CB and ghrelin GHS-R1a receptors may form macromolecular complexes.

Methamphetamine Blocks Adenosine A Receptor Activation via Sigma 1 and Cannabinoid CB Receptors.

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A receptor (AR).

Structure and function of adenosine receptor heteromers.

Adenosine is one of the most ancient signaling molecules and has receptors in both animals and plants. In mammals there are four specific receptors, A, A, A, and A, which belong to the superfamily of G-protein-coupled receptors (GPCRs). Evidence accumulated in the last 20 years indicates that GPCRs are often expressed as oligomeric complexes formed by a number of equal (homomers) or different (heteromers) receptors.

Discovery of a macromolecular complex mediating the hunger suppressive actions of cocaine: Structural and functional properties.

Cocaine not only increases brain dopamine levels but also activates the sigma receptor (σ R) that in turn regulates orexigenic receptor function. Identification of interactions involving dopamine D (D R), ghrelin (GHS-R ), and σ receptors have been addressed by biophysical techniques and a complementation approach using interfering peptides. The effect of cocaine on receptor functionality was assayed by measuring second messenger, cAMP and Ca , levels.

Adenosine A and A Receptors Are Able to Interact with Each Other. A Further Piece in the Puzzle of Adenosine Receptor-Mediated Signaling.

The aim of this paper was to check the possible interaction of two of the four purinergic P1 receptors, the A and the A. Discovery of the A-A receptor complex was achieved by means of immunocytochemistry and of bioluminescence resonance energy transfer. The functional properties and heteromer print identification were addressed by combining binding and signaling assays.

Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB, CB and CB/CB heteromer receptors.

Background: Recent approved medicines whose active principles are ΔTetrahidrocannabinol (Δ-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available.

Adenosine A Receptor Antagonists Affects NMDA Glutamate Receptor Function. Potential to Address Neurodegeneration in Alzheimer's Disease.

(1) Background. -methyl d-aspartate (NMDA) ionotropic glutamate receptor (NMDAR), which is one of the main targets to combat Alzheimer's disease (AD), is expressed in both neurons and glial cells. The aim of this paper was to assess whether the adenosine A receptor (AR), which is a target in neurodegeneration, may affect NMDAR functionality.

Potentiation of cannabinoid signaling in microglia by adenosine A receptor antagonists.

Neuroprotective M2-skewed microglia appear as promising to alter the course of neurodegenerative diseases and G protein-coupled receptors (GPCRs) are potential targets to achieve such microglial polarization. A common feature of adenosine A (A R) and cannabinoid CB (CB R) GPCRs in microglia is that their expression is upregulated in Alzheimer's disease (AD). On the one hand, CB R seems a target for neuroprotection, delaying neurodegenerative processes like those associated to AD or Parkinson's diseases.