Inhalation of phosphoramidon, a neutral endopeptidase inhibitor, induces cough in awake guinea-pigs.
In the present study, we explored whether or not a neutral endopeptidase inhibitor provokes cough in awake guinea-pigs. Inhalation of phosphoramidon at a concentration of 10(-6) M did not cause cough, but increasing the concentration to 10(-5) M caused cough with a latency of about 10 to 12 min. Inhalation of enalapril, an angiotensin-converting enzyme inhibitor, did not cause cough, even at high concentrations of 10(-5) M and 10(-4) M. Pretreatment with phosphoramidon (10(-5) M) significantly increased the number of coughs caused by substance P and capsaicin. Capsaicin-induced coughs were more easily produced in bronchitic guinea-pigs than in normal guinea-pigs. However, there was no significant difference in the number of phosphoramidon-induced coughs between normal and bronchitic guinea-pigs. Phosphoramidon-induced coughs were significantly depressed by codeine (20 mg/kg, p.o.) and CP96345 (2 mg/kg, i.v.). The present results provide new evidence for the proposed idea that neutral endopeptidase may regulate the occurrence of cough.
Takahama
K
K
Department of Pharmacological Sciences, Kumamoto University, Kumamoto, Japan.
Fuchikami
J
J
Kai
H
H
Isohama
Y
Y
Miyata
T
T
D000280:Administration, Inhalation; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000996:Antitussive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000009:adverse effects; D003061:Codeine / Q000494:pharmacology; D003371:Cough / Q000139:chemically induced* / Q000188:drug therapy; D004656:Enalapril / Q000494:pharmacology; D006020:Glycopeptides / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000996:Antitussive Agents; D001713:Biphenyl Compounds; D006020:Glycopeptides; D011480:Protease Inhibitors; D004656:Enalapril; D002211:Capsaicin; C008890:phosphoramidon; D003061:Codeine; C066892:CP 96345