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The role of protease‐activated receptor‐2 (PAR2) in the modulation of beating of the mouse isolated ureter: lack of involvement of mast cells or sensory nerves
Author(s) -
Moffatt J D,
Cocks T M
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702871
Subject(s) - medicine , endocrinology , histamine , receptor , capsaicin , agonist , chemistry , adventitia , biology
The localization of protease‐activated receptor‐2 (PAR2) and the effects of PAR2 activators were investigated in the mouse isolated ureter in order to test the hypothesis that PAR2 activation may initiate neuropeptide release from sensory nerve fibres and hence contribute to inflammation. PAR2 was localized by fluorescence immunohistochemistry to both the smooth muscle and epithelium of the ureter. Macrophage‐like cells in the adventitia of the ureter were also PAR2‐immunoreactive. PAR2‐immunoreactivity was not observed in mast cells or nerve fibres. In circular muscle preparations of the ureter in which continuous rhythmic beating was induced by KCl (20 m M ) and the thromboxane A 2 mimetic U46619 (0.3 μ M ), trypsin (0.3 U ml −1 ) reduced beat frequency to 84.6±2.0% of control rates. The PAR2‐selective peptide agonist SLIGRL‐NH 2 concentration‐dependently (0.1–3.0 μ M ) slowed beat frequency to a maximum of 72.7±2.0%. Histamine (1–300 μ M ) was more efficacious than SLIGRL‐NH 2 in inhibiting ureter beat frequency in a concentration‐dependent manner to a maximum (at 300 μ M ) of 7.9±2.5% of the control rate. Pretreatment of preparations with capsaicin (10 μ M for 30 min) markedly attenuated the inhibitory effect of histamine, but not that of SLIGRL‐NH 2 , indicating a role for sensory nerves in the inhibitory effect of histamine only. The inhibitory effect of SLIGRL‐NH 2 on ureter beat frequency was unaffected by the nitric oxide (NO) synthase inhibitor, L ‐NOARG (100 μ M ) or the cyclo‐oxygenase inhibitor, indomethacin (3 μ M ). In conclusion, PAR2 activation causes inhibition of beating in the mouse ureter that is not mediated by axon reflex release of inhibitory neuropeptides. This inhibitory effect of PAR2 appears to be mediated directly on smooth muscle cells, although the contribution of non‐NO, non‐prostanoid epithelium‐derived factors cannot be ruled out.British Journal of Pharmacology (1999) 128 , 860–864; doi: 10.1038/sj.bjp.0702871