Effects on sleep of microdialysis of adenosine A1 and A2a receptor analogs into the lateral preoptic area of rats

2005 ◽  
Vol 289 (6) ◽  
pp. R1715-R1723 ◽  
Author(s):  
Melvi M. Methippara ◽  
Sunil Kumar ◽  
Md. Noor Alam ◽  
Ronald Szymusiak ◽  
Dennis McGinty
Keyword(s):  
Active Region ◽  
Basal Forebrain ◽  
Preoptic Area ◽  
Brain Areas ◽  
Receptor Stimulation ◽  
Mediated Effects ◽  
Transport Inhibitor ◽  
A2a Receptor ◽  
Adenosine A1 ◽  
Sleep Factor

Evidence suggests that adenosine (AD) is an endogenous sleep factor. The hypnogenic action of AD is mediated through its inhibitory A1 and excitatory A2A receptors. Although AD is thought to be predominantly active in the wake-active region of the basal forebrain (BF), a hypnogenic action of AD has been demonstrated in several other brain areas, including the preoptic area. We hypothesized that in lateral preoptic area (LPOA), a region with an abundance of sleep-active neurons, AD acting via A1 receptors would induce waking by inhibition of sleep-active neurons and that AD acting via A2A receptors would promote sleep by stimulating the sleep-active neurons. To this end, we studied the effects on sleep of an AD transport inhibitor, nitrobenzyl-thio-inosine (NBTI) and A1 and A2A receptor agonists/antagonists by microdialyzing them into the LPOA. The results showed that, in the sleep-promoting area of LPOA: 1) A1 receptor stimulation or inhibition of AD transport by NBTI induced waking and 2) A2A receptor stimulation induced sleep. We also confirmed that NBTI administration in the wake promoting area of the BF increased sleep. The effects of AD could be mediated either directly or indirectly via interaction with other neurotransmitter systems. These observations support a hypothesis that AD mediated effects on sleep-wake cycles are site and receptor dependent.

scholarly journals Corrigendum: Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells

2019 ◽  
Vol 10 ◽  
Author(s):  
Claudia Sorrentino ◽  
Fokhrul Hossain ◽  
Paulo C. Rodriguez ◽  
Rosa A. Sierra ◽  
Antonio Pannuti ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Adenosine A2a Receptor ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Adenosine A2A-Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 Production in Monocytes

2007 ◽  
Vol 104 (2) ◽  
pp. 183-186 ◽  
Author(s):  
Hideo Kohka Takahashi ◽  
Toru Kanke ◽  
Keyue Liu ◽  
Tadashi Yoshino ◽  
Toshiaki Sendo ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Interleukin 18 ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Adenosine A2a

Adenosine A1 receptor blockade selectively potentiates the motor effects induced by dopamine D1 receptor stimulation in rodents

1996 ◽  
Vol 218 (3) ◽  
pp. 209-213 ◽  
Author(s):  
Patrizia Popoli ◽  
Lydia Giménez-Llort ◽  
Antonella Pezzola ◽  
Rosaria Reggio ◽  
Emili Martínez ◽  
...  
Keyword(s):  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Adenosine A1 Receptor ◽  
Receptor Blockade ◽  
Receptor Stimulation ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Motor Effects

Mediation of the cardiovascular response to spinal γ-aminobutyric acidB receptor stimulation by adenosine A1 receptors in anesthetized rats

2000 ◽  
Vol 296 (2-3) ◽  
pp. 153-157 ◽  
Author(s):  
Bum Soo Kim ◽  
Hyun Chul Koh ◽  
Ju Seop Kang ◽  
Harriet Lee ◽  
In Chul Shin ◽  
...  
Keyword(s):  
Cardiovascular Response ◽  
Receptor Stimulation ◽  
Adenosine A1 Receptors ◽  
Anesthetized Rats ◽  
Adenosine A1

Synthesis and Structure Activity Relationships of Chalcone based Benzocycloalkanone Derivatives as Adenosine A1 and/or A2A Receptor Antagonists

Drug Research ◽  
2020 ◽  
Vol 70 (06) ◽  
pp. 243-256
Author(s):  
Helena D. Janse van Rensburg ◽  
Lesetja J. Legoabe ◽  
Gisella Terre’Blanche
Keyword(s):  
Adenosine Receptors ◽  
Methoxy Group ◽  
Hydroxyl Group ◽  
Potential Treatment ◽  
Receptor Antagonists ◽  
Structure Activity ◽  
A2a Receptor ◽  
Adenosine A1 ◽  
Neurological Conditions ◽  
Nanomolar Range

AbstractAdenosine A1 and/or A2A receptor antagonists hold promise for the potential treatment of neurological conditions, such as Parkinson’s disease. Herein, a total of seventeen benzocycloalkanone derivatives were synthesised and evaluated for affinity towards adenosine receptors (A1 and A2A AR). The obtained results allowed for the conclusion that affinity and/or selectivity of the 2-benzylidene-1-indanone and -tetralone derivatives toward A1 and/or A2A ARs may be modulated by the nature of the substituents (either -OH, -OCH3 or morpholine) attached at position C4 of the 1-indanone core and C5 of the 1-tetralone core as well as the meta (C3’) and/or para (C4’) position(s) on ring B. Several compounds (2a–b, 3b–c and 4a–b) possessed affinity for the A1 and/or A2A AR below 10 µM. Additionally, compounds 2a, 3b and 4a were A1 AR antagonists. These results, once again, confirmed the importance of C4 methoxy-group substitution on ring A in combination with meta (C3’) and/or para (C4’) hydroxyl-group substitution ring B of the 2-benzylidene-1-indanone scaffold leading to drug-like compounds 1h and 1j with affinity in the nanomolar-range.

Adenosine A2a receptor stimulation prevents hepatocyte lipotoxicity and non-alcoholic steatohepatitis (NASH) in rats

2012 ◽  
Vol 123 (5) ◽  
pp. 323-332 ◽  
Author(s):  
Chiara Imarisio ◽  
Elisa Alchera ◽  
Salvatore Sutti ◽  
Guido Valente ◽  
Francesca Boccafoschi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Critical Role ◽  
Intraperitoneal Administration ◽  
Adenosine A2a Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Stimulation ◽  
Deficient Diet ◽  
Alcoholic Steatohepatitis ◽  
A2a Receptor ◽  
Adenosine A2a

NEFA (non-esterified ‘free’ fatty acid)-mediated lipotoxicity plays a critical role in the pathogenesis of NASH (non-alcoholic steatohepatitis). In the light of the growing need for new therapeutic options for NASH, we investigated the action of A2aR (adenosine A2a receptor) stimulation against lipotoxicity. The effects of the A2aR agonist CGS21680 [2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxyamidoadenosine] were evaluated ‘in vitro’ in liver cells exposed to SA (stearic acid) and ‘in vivo’ in rats with NASH induced by 8 weeks of feeding with an MCD diet (methionine/choline-deficient diet). In cultured hepatocytes, SA promoted apoptosis by inducing MKK4 (mitogen-activated protein kinase kinase 4)/SEK1 (stress-activated protein kinase/extracellular-signal-regulated kinase kinase-1) and JNK-1/2 (c-Jun N-terminal kinase-1/2) activation. CGS21680 addition prevented JNK-1/2 activation and reduced apoptosis without interfering with lipid accumulation. CGS21680 action required PI3K (phosphoinositide 3-kinase)/Akt-mediated block of MKK4/SEK1. Consistently, PI3K inhibition with wortmannin abolished the cytoprotective action of CGS21680 and reverted MKK4 inhibition. SA lipotoxicity was also prevented by transfecting HTC cells with a specific MKK4/SEK1 siRNA (small interfering RNA). In rats receiving the MCD diet, the development of NASH was associated with MKK4/SEK1 and JNK-1/2 activation. CGS21680 (0.5 mg/kg of body weight, intraperitoneal) administration to MCD-fed rats prevented JNK-1/2 activation by acting on MKK4/SEK1. CGS21680 also effectively reduced NASH-associated ALT (alanine aminotransferase) release, hepatocyte apoptosis, liver inflammation and fibrosis without affecting hepatic steatosis. Taken together, these results demonstrate that, by inhibiting JNK-1/2, A2aR stimulation reduces lipotoxicity and ameliorates NASH, giving a rationale to investigate A2aR agonists as possible new therapeutic agents in preventing fatty liver progression to NASH.

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