In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 314, No. 6 ( 2018-06-01), p. F1077-F1086
Abstract:
Bladder pain is a prominent symptom of interstitial cystitis/painful bladder syndrome. Hydrogen sulfide (H 2 S) generated by cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H 2 S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H 2 S in this model was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H 2 S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H 2 S signaling was upregulated in PAR4-induced bladder pain models, and H 2 S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H 2 S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H 2 S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H 2 S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00526.2017
Language:
English
Publisher:
American Physiological Society
Publication Date:
2018
detail.hit.zdb_id:
1477287-5
