Adenosine A2A receptor controls the gateway of the choroid plexus

Ye, Mengqian; Wang, Mengru; Feng, Yakai; Shang, Huiping; Yang, Yuwen; Hu, Lanxin; Wang, Muran; Vakal, Serhii; Lin, Xiangxiang; Chen, Jiang‐Fan; Zheng, Wu

doi:10.1007/s11302-022-09847-5

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…Interestingly not all CP cells expressed the A 1 receptor, which is similar to a previous study demonstrating heterogenous expression of the glucagon‐like peptide 1 receptor in the CP 30 . Due to technical reasons, we were not able to determine the exact distribution of the A 2 receptor in the CP; however, some studies found it expressed in the rat choroid epithelial cells 22 and in mice CP 34,35 . Altogether these studies demonstrated that these receptors are expressed in the CP and thereby the CP may be a site of action of caffeine.…”

Section: Discussionsupporting

confidence: 84%

“…30 Due to technical reasons, we were not able to determine the exact distribution of the A 2 receptor in the CP; however, some studies found it expressed in the rat choroid epithelial cells 22 in mice CP. 34,35 Altogether these demonstrated that these receptors are expressed in the CP and thereby the CP may be a site of action of caffeine. Future studies with intraventricular injection with caffeine may help to clarify if it is a direct action on the CP that lowers the ICP.…”

Section: Discussionmentioning

confidence: 84%

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Effects of caffeine on intracranial pressure and pain perception in freely moving rats

Israelsen,

Westgate,

Kamp‐Jensen

et al. 2023

Headache

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ObjectiveCaffeine, a non‐selective adenosine receptor (AR) antagonist, is the most consumed psychostimulant in the world. Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known. Therefore, we aimed to investigate the effects of caffeine on ICP and nociceptive responses.MethodsFemale Sprague–Dawley rats were implanted with a novel telemetric device for continuous ICP recordings, which allowed for continuous recordings in freely moving rats. A single dose of caffeine (30 or 120 mg/kg intraperitoneally) was given. In a second group (non‐implanted), the acute effects of 30 mg/kg caffeine on periorbital threshold using Von Frey testing and spontaneous behavior were utilized using an automated behavioral registration platform (Laboratory, Animal, Behavior, Observation, Registration and Analysis System) in a randomized cross‐over study. Quantitative polymerase chain reaction and immunofluorescence were used to localize ARs in the choroid plexus.ResultsA single dose of 30 mg/kg caffeine lowered the ICP by 35% at 165 min after administration (saline: 0.16 ± 0.9 vs caffeine: −1.18 ± 0.9 ΔmmHg, p = 0.0098) and lasted up to 12 h. Administration of 120 mg/kg caffeine showed a faster onset of decrease in ICP within 15 min by 50% (p = 0.0018) and lasted up to 12 h. The periorbital pain thresholds were higher after 1 h (saline: 224.6 ± 15.1 vs caffeine: 289.5 ± 8.7 g, p = 0.005) and lasted up to 5 h. Caffeine‐treated rats had increased locomotor activity, speed, and changed grooming behavior. Expression of AR1 was found in the choroid plexus.ConclusionsThis study demonstrates that caffeine has a lowering effect on ICP as an acute treatment. Interestingly, caffeine acutely caused an increased response in cephalic thresholds supporting hypoalgesic effects. Future studies investigating the beneficial effects of caffeine for elevated ICP are warranted.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 84%

Effects of caffeine on intracranial pressure and pain perception in freely moving rats

Israelsen,

Westgate,

Kamp‐Jensen

et al. 2023

Headache

View full text Add to dashboard Cite

show abstract

“…Additionally, A 2A R activity in the choroid plexus was found possibly to serve as a therapeutic target for controlling the gateway function of this plexus which is able to remodel immune homeostasis in the CNS, with implications for the treatment of neuroimmunological disorders [25]. The P2X7R was initially demonstrated to contribute to the antitumor activity of atractylenolide I (an immunology inhibitor) in human cervical cancer cells [26].…”

mentioning

confidence: 99%