[The effect of inhaled ipratropium bromide on airway and lung tissue muscarinic receptors in a rat model of COPD].
OBJECTIVE
To observe the effect of inhaled ipratropium bromide on airway and lung tissue muscarinic receptors (MR) in a rat model of chronic obstructive pulmonary disease (COPD).


METHODS
The rat model of COPD was established by chronic exposure with high concentrations of SO(2) gas, COPD rats inhaled aerosolized 0.025% ipratropium bromide solution 10 ml (twice/d, 20min/time). The MR was determined by radioligand binding studies with (3)H-QNB as the ligand.


RESULTS
Compared with that of control, there was a marked increase in MR density on day 30 of treatment with ipratropium but not on day 5. The MR density decreased and close to normal level on the 6th day after cessation of regular therapy with inhaled ipratropium for 30 days. No significant difference was observed in antagonist affinity (Kd) among different time groups of ipratropium therapy.


CONCLUSIONS
Chronic exposure to the anticholinergic agent ipratropium bromide produces an up-regulation of airway MR. The airway MR density can recover to normal when treatment stopped. Up-regulation of airway MR is associated with transient bronchoconstriction following cessation of regular ipratropium therapy and lung function deteriorated following long-term inhaled ipratropium bromide.
Yao
W
W
Department of Respiratory Medicine, the Third Hospital, Beijing Medical University, Beijing 100083.
Wang
G
G
Zhu
H
H
Zhao
M
M
D000280:Administration, Inhalation; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D009241:Ipratropium / Q000008:administration & dosage*; D008168:Lung / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects*; D014132:Trachea / Q000737:chemistry / Q000187:drug effects*; D015854:Up-Regulation
D001993:Bronchodilator Agents; D011976:Receptors, Muscarinic; D009241:Ipratropium