Effect of Thiorphan on the Response of Guinea-Pig Isolated Urinary Bladder to Exogenous and Endogenous Tachykinins

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Abstract
Thiorphan, a well known inhibitor of ''enkephalinase'' (indopeptidase 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 htis effect was evident both in presence and absence of the mucosal layer. Thirphan also enhanced and porlonged 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 bladder and modulates the intensity of the biological response produced after their release from peripheral endings of sensory nerves.

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