Abstract
1. Experiments were designed to determine whether regional differences exist in the effects of phosphoramidon (a metalloprotease inhibitor) and [ d-Arg, 1 d-Pro, 2 d-Trp, 7,9Leu, 11]-substance P (a tachykinin antagonist: rpwwL-SP) on contractile responses to electrical field stimulation (EFS) in rabbit airways. 2. EFS contractions were potentiated by phosphoramidon and were attenuated by rpwwL-substance P at low frequencies (less than 10 Hz). 3. Potentiating effect of phosphoramidon was more pronounced in distal bronchus than trachea and was proportional to total proteinase activity. 4. The rank order of inhibitory effect of rpwwL-SP was: trachea > proximal bronchus > distal bronchus, and inverse relationship was observed between the drug's inhibitory effect of drug and total proteinase activity in three different regions. 5. Good correlation was observed between total proteinase activity and p D 2 value of neurokinin A in each airway region. 6. In conclusion, tachykinin modulates acetylcholine release in the contractile response to EFS at low frequencies (less than 10Hz), and regional differences in the effects of the inhibitor and the antagonist on EFS-evoked contractions in the rabbit airway were suggested to be due to heterogenous distribution of the metalloprotease which metabolized tachykinins.
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