Circadian variation of [3H]N6-(l-phenylisopropyl)adenosine binding in rat brain

doi:10.1016/0304-3940(84)90445-2

Neuroscience Letters

Volume 46, Issue 2, 4 May 1984, Pages 219-222

https://doi.org/10.1016/0304-3940(84)90445-2 Get rights and content

Abstract

Since considerable recent experimental evidence suggests a role for the purine nucleoside adenosine in the regulation of mammalian sleep, circadian variations of adenosine receptor binding were examined in whole rat brain using [³H]N⁶-l-phenylisopropyl)adenosine ([³H]l-PIA). These results demonstrate a significant circadian variation in the number of [³H]l-PIA. binding sites (B_max) with a maximum 3 h after the beginning of the dark phase of a $12 h light 12 h dark cycle$ , and a minimum 8 h later (P < 0.025). The dissociation constant (K_d) of [³H]l-PIA at adenosine receptors did not exhibit any statistically significant circadian variation. These data indicate a daily rhythm in the number of adenosine receptors without a change in K_d and may support the hypothesized involvement of adenosine in the regulation of sleep in rats.

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Recent studies show that neuroglial interactions play a key role in the regulation of complex behavior. Of particular importance is adenosine-mediated fine-tuning of glutamate neurotransmission, which modulates sleep, circadian rhythms, and alcohol intake. Astrocytic, soluble N-ethyl maleimide-sensitive fusion protein attachment protein receptor-mediated ATP release provides the extracellular adenosine that drives homeostatic sleep. Adenosine gates both photic (light-induced) glutamatergic and nonphotic (behavioral) input to the circadian clock located in the suprachiasmatic nucleus of the hypothalamus. Acute ethanol increases extracellular adenosine, which mediates the ataxic and hypnotic/sedative effects of alcohol, while chronic ethanol reduces adenosine tonus, leading to insomnia, a major predictor of relapse. Studies using mice lacking equilibrative nucleoside transporter 1 have illuminated how adenosine functions through neuroglial interactions involving glutamate uptake transporter GLT-1 (referred to as excitatory amino acid transporter 2, or EAAT2, in humans) and possibly water channel aquaporin 4 to regulate ethanol sensitivity, reward-related motivation, and alcohol intake.
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Citation Excerpt :
The adenosine system responds in a regulatory manner, dependent on daytime or sleep deprivation. Extracellular adenosine, but also a number of adenosine receptors follow a daily rhythm with a maximum in the beginning of the dark phase, when cortical adenosine is low and the activities of the adenosine synthesizing 5′-nucleotidase and S-adenosylhomocysteine hydrolase start to increase (Chagoya de Sanchez et al., 1993; Porkka-Heiskanen et al., 2000; Virus et al., 1984). The adenosine concentration is associated with local changes in energy (Porkka-Heiskanen and Kalinchuk, 2011).
Purinergic neurotransmission, involving release of ATP as an efferent neurotransmitter was first proposed in 1972. Later, ATP was recognised as a cotransmitter in peripheral nerves and more recently as a cotransmitter with glutamate, noradrenaline, GABA, acetylcholine and dopamine in the CNS. Both ATP, together with some of its enzymatic breakdown products (ADP and adenosine) and uracil nucleotides are now recognised to act via P2X ion channels and P1 and P2Y G protein-coupled receptors, which are widely expressed in the brain. They mediate both fast signalling in neurotransmission and neuromodulation and long-term (trophic) signalling in cell proliferation, differentiation and death. Purinergic signalling is prominent in neurone–glial cell interactions. In this review we discuss first the evidence implicating purinergic signalling in normal behaviour, including learning and memory, sleep and arousal, locomotor activity and exploration, feeding behaviour and mood and motivation. Then we turn to the involvement of P1 and P2 receptors in pathological brain function; firstly in trauma, ischemia and stroke, then in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's, as well as multiple sclerosis and amyotrophic lateral sclerosis. Finally, the role of purinergic signalling in neuropsychiatric diseases (including schizophrenia), epilepsy, migraine, cognitive impairment and neuropathic pain will be considered.
Adenosine A<inf>1</inf> receptors regulate the response of the hamster circadian clock to light
2001, European Journal of Pharmacology
Circadian rhythms are synchronized to the environmental light–dark cycle by daily, light-induced adjustments in the phase of a biological clock located in the suprachiasmatic nucleus. Ambient light alters the phase of the clock via a direct, glutamatergic projection from retinal ganglion cells. We investigated the hypothesis that adenosine A₁ receptors modulate the phase adjusting effect of light on the circadian clock. Systemic administration of the selective adenosine A₁ receptor agonist, N⁶-cyclohexyladenosine (CHA), significantly (p<0.05) attenuated light-induced phase delays and advances of the circadian activity rhythm. Selective agonists for the adenosine A_2A and adenosine A₃ receptors were without effect. The inhibitory effect of CHA on light-induced phase advances was dose-dependent (0.025–1.0 mg/kg, ED₅₀=0.3 mg/kg), and this effect was blocked in a dose-dependent (0.005–1.0 mg/kg) manner by the adenosine A₁ receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Injection of CHA (10 μM) into the region of the suprachiasmatic nucleus significantly attenuated light-induced phase advances, and this effect was also blocked by DPCPX (100 μM). The results suggest that adenosine A₁ receptors located in the region of the suprachiasmatic nucleus regulate the response of the circadian clock to the phase-adjusting effects of light.
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1994, Pharmacology and Therapeutics
The circadian cycle of sleep and wakefulness in humans is controlled by the activity of many neurotransmitters. Studies of the effects of drugs on the central nervous system have elucidated some of the mechanisms that may be involved. Some transmitters are concerned with the basic control of sleep and wakefulness, influencing both alertness during the day and the pattern of nocturnal sleep. On the other hand, there are other transmitters that appear to be concerned primarily with the manifestation of wakefulness and vigilance, without a direct role in the process of sleep.
Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat - possible physiological significance for the energetic homeostasis and the sleep-wake cycle
1993, Brain Research
The role of adenosine as a metabolic regulator of physiological processes in the brain was studied by measuring its concentrations and the activity of adenosine-metabolizing enzymes: 5′-nucleotidase,S-adenosylhomocysteine hydrolase, adenosine deaminase and adenosine kinase in the cerebral cortex of the rat. Other purine compounds, such as, inosine, hypoxanthine and adenine nucleotides were also studied. The purines' pattern was bimodal with high levels of adenosine, inosine and hypoxanthine during the light period reaching their peak at 12.00 h, 08.00 h and 16.00 h, respectively, and small increments during the night between 02.00 h and 04.00 h. The enzymatic activities showed, in general, an unimodal profile with low activity during the day and high activities at night. The adenine nucleotide profile showed a significant diminution between 12.00 h and 24.00 h. The high adenosine level during the day might be due to a diminution of adenine nucleotide and to the low activity of adenosine-metabolizing enzymes, suggesting an accumulation of the nucloside. The night increase, although of less magnitude, is simultaneous to high activity of adenosine-metabolizing enzymes and could be due to an increased formation of the nucleoside. The present data and the findings from other authors strongly suggest that adenosine in the brain cortex of the rat can participate at least in two physiological process: regulation of the sleep-wake cycle and replenishment of the adenine nucleotide pool.
Purine receptors and their pharmacological roles
1989, Advances in Drug Research

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Circadian variation of [3H]N6-(l-phenylisopropyl)adenosine binding in rat brain

Abstract

J. biol. Chem.

Circadian variations of adenosine and its physiological meaning in the energetic homeostasis of the cell and the sleep-wake cycle of the rat

Preliminary data on the possible hypnogenic role of adenosine

J. Neurochem.

Circadian rhythms in rat brain neurotransmitter receptors

The role of adenosine and its nucleotides in central synaptic transmission

Progr. Neurobiol.

Circadian variation of [³H]N⁶-(l-phenylisopropyl)adenosine binding in rat brain