Spontaneously released substance P and bradykinin from isolated guinea-pig bladder.
OBJECTIVE
To investigate whether the isolated urinary bladder spontaneously 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.


METHODS
Urinary bladder segments (2 x 10 x 0.8-1 mm) were isolated from guinea pigs and studied in vitro; tissue contraction was assessed using force-displacement transducers and the release of peptides by specific enzyme immunoassays.


RESULTS
In the absence of any exogenous agonists, the inhibition of neutral endopeptidase and angiotensin-converting enzyme by phosphoramidon and captopril, respectively, increased the frequency and magnitude of spontaneous motility of isolated bladder strips. Phosphoramidon increased the net release of SP-like immunoreactivity (SP-LI) and captopril increased the net release of SP-LI and BK-LI, concomitant with contraction. Peptide-LI was recovered primarily from bladder mucosa and to a lesser degree from detrusor smooth muscle. Similarly, peptidase inhibitors primarily affected the bladder mucosa; phosphoramidon induced a fourfold increase in SP-LI and captopril induced a significant increase of SP-LI and BK-LI from the mucosa. Tissues contracted in response to peptidase inhibitors in the presence of atropine and indomethacin, but contraction was reduced significantly by in vitro capsaicin desensitization or removal of bladder mucosa. BK stimulated SP-LI release from mucosa but not detrusor. SP stimulated increased BK-LI release from mucosa and detrusor.


CONCLUSIONS
These findings indicate the basal release of peptide-like immunoreactivity by isolated bladder and further support the concept that peptidases located in the bladder mucosa are important in terminating the effects of endogenous peptides.
Saban
R
R
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA.
Franz
J
J
Bjorling
D E
DE
D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D009119:Muscle Contraction; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*
D006020:Glycopeptides; D011480:Protease Inhibitors; D013373:Substance P; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin; C008890:phosphoramidon