Effect of thiorphan on the response of guinea-pig isolated urinary bladder to exogenous and endogenous tachykinins.
Thiorphan, a well known inhibitor of 'enkephalinase' (endopeptidase 24.11) potentiated and prolonged the contractile response to substance P (SP) and neurokinin A (NKA) on strips of the guinea-pig isolated urinary bladder and this effect was evident both in presence and absence of the mucosal layer. Thiorphan also enhanced and prolonged the capsaicin-induced contraction in strips from the bladder dome which is thought to be mediated by release of endogenous tachykinins. Exposure to capsaicin produced simultaneous release of SP- and tachykinin-like immunoreactivity both in presence and absence of mucosa. This effect of capsaicin was potentiated by thiorphan. Endopeptidase 24.11 activity was detected in the guinea-pig urinary bladder, being more concentrated in the mucosal than the muscular layer. These findings indicate that endopeptidase 24.11 terminates the activity of tachykinins in the guinea-pig urinary bladder and modulates the intensity of the biological response produced after their release from peripheral endings of sensory nerves.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Astolfi
M
M
Santicioli
P
P
Tramontana
M
M
Leoncini
G
G
Geppetti
P
P
Giachetti
A
A
Meli
A
A
D000818:Animals; D004357:Drug Synergism; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology; D015320:Tachykinins / Q000494:pharmacology*; D015244:Thiorphan / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D015320:Tachykinins; D015244:Thiorphan; D015260:Neprilysin