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Tytuł:
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Suppression of adenosine A 2a receptors alleviates bladder overactivity and hyperalgesia in cyclophosphamide-induced cystitis by inhibiting TRPV1.
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Autorzy:
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Yang Y; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Zhang H; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Lu Q; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Liu X; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Fan Y; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Zhu J; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Sun B; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Zhao J; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Dong X; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China. Electronic address: .
Li L; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China. Electronic address: .
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Źródło:
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Biochemical pharmacology [Biochem Pharmacol] 2021 Jan; Vol. 183, pp. 114340. Date of Electronic Publication: 2020 Nov 13.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
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MeSH Terms:
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Adenosine A2 Receptor Antagonists/*therapeutic use
Cyclophosphamide/*toxicity
Cystitis/*drug therapy
Hyperalgesia/*drug therapy
TRPV Cation Channels/*antagonists & inhibitors
Urinary Bladder, Overactive/*drug therapy
Adenosine A2 Receptor Antagonists/pharmacology ; Animals ; Antineoplastic Agents, Alkylating/toxicity ; Cystitis/chemically induced ; Cystitis/metabolism ; Female ; Hyperalgesia/chemically induced ; Hyperalgesia/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Adenosine A2A/biosynthesis ; TRPV Cation Channels/biosynthesis ; Triazines/pharmacology ; Triazoles/pharmacology ; Urinary Bladder/drug effects ; Urinary Bladder/metabolism ; Urinary Bladder, Overactive/chemically induced ; Urinary Bladder, Overactive/metabolism
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Contributed Indexing:
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Keywords: A(2a) receptor; Afferent pathway; Bladder overactivity; Hyperalgesia; TRPV1
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Substance Nomenclature:
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0 (Adenosine A2 Receptor Antagonists)
0 (Antineoplastic Agents, Alkylating)
0 (Receptor, Adenosine A2A)
0 (TRPV Cation Channels)
0 (Triazines)
0 (Triazoles)
0 (Trpv1 protein, rat)
0 (ZM 241385)
8N3DW7272P (Cyclophosphamide)
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Entry Date(s):
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Date Created: 20201115 Date Completed: 20210415 Latest Revision: 20210415
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Update Code:
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20240105
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DOI:
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10.1016/j.bcp.2020.114340
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PMID:
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33189675
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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a type of chronic bladder inflammation characterized by increased voiding frequency, urgency and pelvic pain. The sensitization of bladder afferents is widely regarded as one of the pathophysiological changes in the development of IC/BPS. There is evidence that adenosine A 2a receptors are involved in regulating the sensitization of sensory afferents. However, the effect of adenosine A 2a receptors on cystitis remains unknown. In the present study, a rat model of chronic cystitis was established by intraperitoneal injection with cyclophosphamide (CYP). Cystometry and behavioral tests were performed to investigate bladder micturition function and nociceptive pain. The rats with chronic cystitis showed symptoms of bladder overactivity, characterized by an increase in bladder voiding frequency and voiding pressure. CYP treatment significantly increased the expression of the A 2a receptor in bladder afferent fibers and dorsal root ganglion (DRG) neurons. The A 2a receptor antagonist ZM241385 prevented bladder overactivity and hyperalgesia elicited by CYP-induced cystitis. In addition, the A 2a receptor and TRPV1 were coexpressed on DRG neurons. The TRPV1 antagonist capsazepine blocked bladder overactivity induced by the A 2a receptor agonist CGS21680. In contrast, ZM241385 significantly inhibited the capsaicin-induced increase in intracellular calcium concentration in DRG neurons. These results suggest that suppression of adenosine A 2a receptors in bladder afferents alleviates bladder overactivity and hyperalgesia elicited by CYP-induced cystitis in rats by inhibiting TRPV1, indicating that the adenosine A 2a receptor in bladder afferents is a potential therapeutic target for the treatment of IC/BPS.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
