Effects in vitro and in vivo of thioureas on acetylcholine esterase activity of rat tissues

Abstract

In view of data available that accumulation of acetylcholine in the lung leads to pulmonary edema formation, the effects of thiourea (TU), phenylthiourea (PTU) and α-naphthylthiourea (ANTU) on lung acetylcholine esterase (AchE) activity were examined in vitro and in vivo. ANTU and PTU produced a concentration-dependent inhibition of lung AchE activity in vitro. The Sped 50 values of ANTU and PTU were 2.8 × 10 −4 and 5 × 10 −4 M respectively. No significant inhibition in AchE activity of the lung occurred in response to any concentration of TU. The mechanisms of AchE inhibition due to ANTU appeared to be competitive. The apparent K m for lung AchE averaged 7.23 × 10 −4 M and the K i for ANTU averaged 1.11 × 10 −4 M. ANTU at 5 × 10 −4 M inhibited the AchE activity of all examined tissues in vitro. An edema-producing dose of ANTU had no effect on AchE activity of any tissue except the brain. A failure to demonstrate the inhibitory effect in vivo of ANTU on AchE activity has been discussed in this paper. Pretreatment with atropine offered no protection against the pulmonary edema-producing ability of ANTU. The data collected in the present report indicate that inhibition of lung AchE is probably not the mechanism of ANTU-induced pulmonary edema. The significance of brain AchE inhibition in response to an edema-producing dose of ANTU is not known.