A regional difference of the effect of tachykinin on cholinergic response evoked by electrical field stimulation in the rabbit airway.
1. Experiments were designed to determine whether regional differences exist in the effects of phosphoramidon (a metalloprotease inhibitor) and [D-Arg,1D-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 pD2 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 10 Hz), 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.
Funayama
N
N
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Goroumaru-Shinkai
M
M
Takayanagi
I
I
D000109:Acetylcholine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D010450:Endopeptidases / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors; D015288:Neurokinin A / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins; D012137:Respiratory System / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D006020:Glycopeptides; D011994:Recombinant Proteins; D015320:Tachykinins; D013373:Substance P; C050702:substance P, Arg(1)-Pro(2)-Trp(7,9)-Leu(11)-; D015288:Neurokinin A; D010450:Endopeptidases; D015260:Neprilysin; D000109:Acetylcholine; C008890:phosphoramidon