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Prostaglandins, Adenosine, and Histaminergic System in the Regulation of Sleep and Wakefulness

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Sleep and its Disorders

Part of the book series: Translational Medicine Research ((TRAMERE))

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Abstract

This chapter provides an overview of the current knowledge about the roles of prostaglandins, adenosine, and the histaminergic system in sleep–wake regulation, focusing on prostaglandins, adenosine, and histamine in the central nervous system, their level regulation, their receptors, and pharmacological and molecular biological manipulations of the adenosine and histaminergic systems. Prostaglandin (PG) D2 is an endogenous somnogen that can increase the extracellular adenosine under the subarachnoid space of the basal forebrain, thereby induce physiological sleep. Adenosine is found neither stored nor released as a classical neurotransmitter, which is formed inside cells or on their surface and derived from adenine nucleotide breakdown. Prolonged wakefulness increases extracellular adenosine concentration in the cortex and basal forebrain and the concentration will go back during the sleep recovery period. Therefore, adenosine has been thought of as a homeostatic regulator of sleep and a link between the humoral and neural mechanisms of sleep–wake regulation. Both the adenosine A1 receptor (A1R) and the A2AR are involved in sleep induction. The somnogenic effects of PGD2 are predominantly dependent on A2AR. In addition, it is proved that the A2AR is necessary for the arousal effect of caffeine by using gene-manipulated mice. In contrast, the role of the A1R is more complicated. Although stimulation of A1R in wake-promoting brain areas increases sleep, activation of A1R in the lateral preoptic area induces wakefulness, indicating that the A1R acts in a site-dependent manner in sleep–wake regulation. The histaminergic system also plays an essential role in sleep–wake regulation and is indispensable for the sleep/wakefulness-promoting effects induced by the A1R and A2AR. A brief discussion about the potential therapeutic applications of agonists and antagonists of these receptors in sleep disorders is also included at the end of this chapter.

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Abbreviations

ADA:

Adenosine deaminase

AK:

Adenosine kinase

ATP:

Adenosine triphosphate

cAMP:

Cyclic adenosine 3′, 5′-monophosphate

cN:

Cytosolic nucleotidase

CPA:

N6-cyclopentyladenosine

CSF:

Cerebrospinal fluid

dnSNARE:

The SNARE domain of the protein synaptobrevin II

DP1R:

PGD2 receptor

GPCR:

G protein-coupled receptors

H1R:

Histamine H1 receptor

H-PGDS:

Hematopoietic PGDS

KO:

Knockout

L-PGDS:

Lipocalin-type PGDS

NBTI:

S-(4-nitrobenzyl)-6-thioinosine

NREM:

Non-rapid eye movement

PLC:

Phospholipase C

PG:

Prostaglandin

PGDS:

PGD synthase

R:

Receptor

REM:

Rapid eye movement

SAHH:

S-adenosyl-homocysteine hydrolase

Se4+:

Tetravalent selenium

SeCl4:

Selenium tetrachloride

SWA:

Slow wave activity

TMN:

Tuberomammillary nucleus

VLPO:

Ventrolateral preoptic area

WT:

Wild type

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  1. Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China

    Zhi-Li Huang, Ze Zhang & Wei-Min Qu

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  1. Zhi-Li Huang
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  2. Ze Zhang
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  3. Wei-Min Qu
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Correspondence to Zhi-Li Huang .

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  1. John Miclot Professor, Division of Sleep Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Allan I. Pack

  2. Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Qing Yun Li

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Huang, ZL., Zhang, Z., Qu, WM. (2022). Prostaglandins, Adenosine, and Histaminergic System in the Regulation of Sleep and Wakefulness. In: Pack, A.I., Li, Q.Y. (eds) Sleep and its Disorders. Translational Medicine Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-2168-2_3

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