Regional differences of the contractile responses to acetylcholine and neurokinin A in rabbit airway: heterogeneous distribution of the metabolic enzymes.
1. Experiments were designed to determine whether differences exist in the sensitivity to muscarinic and tachykinin agonists in rabbit airways. 2. The rank order of sensitivity (pD2 value) to acetylcholine was: trachea > proximal bronchus > distal bronchus, whereas no regional difference was observed in the sensitivity to carbamylcholine which is resistant to acetylcholinesterase. 3. Acetylcholinesterase activity was greater in the distal than in the proximal airway. 4. In the absence of the peptidase inhibitor, phosphoramidon, the pD2 values of neurokinin A (NKA) and substance P (SP) in trachea were significantly greater than that in bronchus, whereas no regional difference was observed in the NK1 selective agonist, substance P methyl ester (SPOMe). 5. Application of phosphoramidon (10 microM) to avoid peptide degradation abolished the regional difference of the pD2 values of SP. 6. In conclusion, regional differences in sensitivities to acetylcholine and NKA in the rabbit airway were suggested to be due to distribution to the metabolic enzymes of these drugs.
Goroumaru-Shinkai
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Yamamoto
R
R
Funayama
N
N
Takayanagi
I
I
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology; D015288:Neurokinin A / Q000494:pharmacology*; D011817:Rabbits; D012137:Respiratory System / Q000187:drug effects* / Q000201:enzymology; D015320:Tachykinins / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D015320:Tachykinins; D015288:Neurokinin A; D002217:Carbachol; D000110:Acetylcholinesterase; D000109:Acetylcholine