3.4 Release of SP and PGE2 contribute to
H2O2-induced enhancement effects
Tachykinins are neuropeptides present in the capsaicin-sensitive primary
afferents of the urinary bladder of various species (including humans).
Release of these peptides in the periphery produced prominent effects on
the SBCs of isolated bladder strips[3]. In agreement with this
report, application of SP (500nM) increased the SBCs of human-bladder
strips significantly (Fig. 5A), and the enhancing effect of SP could be
blocked by a specific antagonist of
NK2Rs: SR 48968 (10μM). AUC and Δg
were reduced by 84.5% and 64.3%, respectively (Fig. 5A, B). NK2R is
the main subtype of neurokinin receptor that mediates the effects of
neurokinins in the human bladder[40-42]. SR 48968 applied alone did
not impact the contractile activity. As expected, the NK2R antagonist
SR 48968 (10μM) reduced the
H2O2(100μM)-induced increase in SBCs
significantly (Fig. 5C). AUC and Δg were reduced by 74.1% and 49.1%,
respectively (Fig. 5D), which suggested that SP release contributed to
the enhancement effects of H2O2.
PGE2 released from sensory afferents, urothelial cells, or the detrusor
has been shown have important modulatory effects on SBCs in
vitro [43] and voiding behavior in vivo [44]. In agreement
with those reports, application of PGE2 (1μM) evoked a significant
increase in the SBCs of human-bladder strips (Fig. 6A).
Pretreatment (15 min before
H2O2) with indomethacin (10μM) to block
the synthesis and release of PGE2 led to significant attenuation of
H2O2 (100μM)-induced effects, with AUC
and Δg being reduced by 65.9% and 35.9%, respectively (Fig. 6B and C).
Indomethacin (10μM) applied alone did not affect contractile activity.
This observation indicated that PGE2 release contributed to the
enhancing effects of H2O2.