Prostanoid-dependent bladder pain caused by proteinase-activated receptor-2 activation in mice: Involvement of TRPV1 and T-type Ca 2+ channels

• Published in: Journal of pharmacological sciences 2018-01, Vol.136 (1), p.46-49
• Main Authors: Tsubota, Maho, Ozaki, Tomoka, Hayashi, Yuko, Okawa, Yasumasa, Fujimura, Ayaka, Sekiguchi, Fumiko, Nishikawa, Hiroyuki, Kawabata, Atsufumi
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Calcium Channels, T-Type - metabolism; Calcium Channels, T-Type - physiology; Cells, Cultured; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; Female; Humans; Hyperalgesia - chemically induced; Hyperalgesia - genetics; Hyperalgesia - prevention & control; Indomethacin; Mice, Inbred Strains; Nociceptive Pain - chemically induced; Nociceptive Pain - genetics; Nociceptive Pain - prevention & control; Oligopeptides - pharmacology; Receptor, PAR-2 - metabolism; Receptor, PAR-2 - physiology; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism; TRPV Cation Channels - physiology; Urinary Bladder
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2017.12.007

We studied the pronociceptive role of proteinase-activated receptor-2 (PAR2) in mouse bladder. In female mice, intravesical infusion of the PAR2-activating peptide, SLIGRL-amide (SL), caused delayed mechanical hypersensitivity in the lower abdomen, namely 'referred hyperalgesia', 6-24 h after the administration. The PAR2-triggered referred hyperalgesia was prevented by indomethacin or a selective TRPV1 blocker, and restored by a T-type Ca channel blocker. In human urothelial T24 cells, SL caused delayed prostaglandin E production and COX-2 upregulation. Our data suggest that luminal PAR2 stimulation in the bladder causes prostanoid-dependent referred hyperalgesia in mice, which involves the activation of TRPV1 and T-type Ca channels.