Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Coelho, A (Author) Other; Wolf Johnston, AS (Author) Other; Shinde, S (Author) Other; Cruz C.D. (Author) FMUP; Francisco Cruz (Author) FMUP; António Avelino Silva (Author) FMUP; Birder, LA (Author) Other

Journal

Title: British Journal of Pharmacology

Vol. 172

Pages: 1691-1699

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 33 Citations

Scopus - 35 Citations

Other information

Authenticus ID: P-00A-9TA

DOI: 10.1111/bph.12958

Abstract (EN): Background and PurposeThe urinary bladder urothelium expresses various receptors and in response to chemical and mechanical stimuli releases mediators, thereby modulating bladder sensory pathways. Transient receptor potential vanilloid 1 (TRPV1) ion channels and nerve growth factor (NGF) in those cells are implicated in this modulatory effect and play a role in sensitizing pain-related afferent pathways during inflammation. In this study, we investigated the interaction between NGF and TRPV1 channels in urothelial cells. Experimental ApproachUrothelial cells from female Sprague-Dawley rat bladders were cultured to quantify membrane expression of TRPV1 channels and capsaicin-induced ATP release in the presence of NGF alone or with TrKA or PI3K inhibitors. Pain scores from rats with cyclophosphamide (CYP)-induced bladder inflammation were assessed after treatment with a TrkA antagonist. Bladders (from control and CYP rats) were collected and analysed for NGF content and TRPV1 channel expression. Key ResultsCultured cells responded to NGF with increased TRPV1 channel expression in the cell membrane and increased release of ATP. Both responses were blocked by either a TrkA antagonist or a PI3K inhibitor. Treatment in vivo with the TrkA antagonist alleviated pain symptoms and reduced CYP-induced NGF overexpression in the mucosa. Furthermore, in urothelial cells from animals with bladder inflammation, expression of TRPV1 channels in the membrane was significantly increased. Conclusions and ImplicationsDuring bladder inflammation, increased production of NGF in urothelial cells induced increased expression and activity of TRPV1 channels in the cell membrane. This effect was primarily mediated by the PI3K pathway.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9