SPONTANEOUSLY RELEASED SUBSTANCE-P AND BRADYKININ FROM ISOLATED GUINEA-PIG BLADDER

Objectives To investigate whether the isolated urinary bladder spontan eously releases substance P (SP) or bradykinin (BK), which can act as potent mediators of pain and inflammation of the urinary bladder, and whether peptidase inhibitors enhance peptide release. Materials and me thods Urinary bladder segments (2 x 10 x 0.8-1 mm) were isolated from guinea pigs and studied in vitro; tissue contraction was assessed usin g force-displacement transducers and the release of peptides by specif ic enzyme immunoassays. Results In the absence of any exogenous agonis ts, the inhibition of neutral endopeptidase and angiotensin-converting enzyme by phosphoramidon and captopril, respectively, increased the f requency and magnitude of spontaneous motility of isolated bladder str ips. Phosphoramidon increased the net release of SP-like immunoreactiv ity (SP-LI) and captopril increased the net release of SP-LI and BK-LI , concomitant with contraction. Peptide-LI was recovered primarily fro m bladder mucosa and to a lesser degree from detrusor smooth muscle. S imilarly, peptidase inhibitors primarily affected the bladder mucosa; phosphoramidon induced a fourfold increase in SP-LI and captopril indu ced a significant increase of SP-LI and BK-LI from the mucosa. Tissues contracted in response to peptidase inhibitors in the presence of atr opine and indomethacin, but contraction was reduced significantly by i n vitro capsaicin desensitization or removal of bladder mucosa. BK sti mulated SP-LI release from mucosa but not detrusor. SP stimulated incr eased BK-LI release from mucosa and detrusor. Conclusions These findin gs indicate the basal release of peptide-like immunoreactivity by isol ated bladder and further support the concept that peptidases located i n the bladder mucosa are important in terminating the effects of endog enous peptides.