Administration of recombinant enkephalinase (neutral endopeptidase) prevents capsaicin-induced miosis in the rabbit eye in vivo.

Substance P induced a dose-dependent contraction of iris sphincter muscles when applied in the presence of atropine to the isolated rabbit iris in vitro as evidenced by a decreased pupil diameter. Pretreatment of the iris with 20 micrograms of recombinant enkephalinase (neutral endopeptidase; EC 3.4.24.11) totally abolished the contractile response to substance P. Injection of 10 micrograms of capsaicin into the anterior chamber of atropine-treated rabbit eyes in vivo induced an immediate and intense miosis. Injection of 100 micrograms of recombinant enkephalinase, 1 or 5 min before capsaicin injection, significantly inhibited this miosis. This effect of enkephalinase was totally abolished by preincubating the enzyme with thiorphan, a high-affinity enkephalinase inhibitor. These results show that enkephalinase, which is known to hydrolyze substance P in vitro with high efficiency, also hydrolyzes endogenously released substance P in vivo. Furthermore, our results suggest that enkephalinase application may represent a novel therapeutic approach to treat substance P-mediated pathologies.