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- Title
Different Effects Of β -Adrenoceptor Desensitization On Inhibitory Actions In Guinea-Pig Trachealis.
- Authors
Mizutani, Hiroshi; Kume, Hiroaki; Ito, Yasushi; Takagi, Kenzo; Yamaki, Kenichi
- Abstract
SUMMARY 1. To determine the inhibitory effects of agents that pass through and bypass β -adrenoceptors under conditions of tolerance to β -adrenoceptor agonists, we examined the inhibition by the β -adrenoceptor agonists forskolin and theophylline against contraction induced by methacholine (MCh) after exposure to higher concentrations of a β -adrenoceptor agonist for a long time in guinea-pig tracheal smooth muscle, using isometric tension records. 2. After exposure to procaterol (0.0003–3 μ mol/L) for 45 min, the inhibitory effect of 0.03 μ mol/L procaterol on 1 μ mol/L MCh-induced contraction was attenuated in a concentration-dependent manner, whereas after exposure to isoprenaline (0.0003–3 μ mol/L) for an equivalent time, the inhibitory effect of isoprenaline was markedly attenuated at each concentration. However, after exposure to 3 μ mol/L procaterol for 45 min, the inhibitory actions of forskolin and theophylline were, conversely, augmented. 3. These phenomena were observed under conditions whereby the response to MCh returned to control levels 6 h after removal of 3 μ mol/L procaterol. The percentage inhibition produced by 0.1 μ mol/L forskolin against 1 μ mol/L MCh after exposure to normal bathing solution or 3 μ mol/L procaterol for 45 min was 9.8 ± 5.5 and 82.8 ± 6.5%, respectively (P < 0.001). These values for 100 μ mol/L (18 μ g/mL) theophylline on MCh resposnes were 9.9 ± 8.5 and 88.0 ± 4.4% (n = 6 for both), respectively (P < 0.001). 4. The inhibitory action of agents that bypass β -adrenoceptors was markedly augmented under conditions of β -adrenoceptor desensitization in airway smooth muscle. 5. In conclusion, procaterol is less potent in causing desensitization of β -adrenoceptors than isoprenaline. The activity of adenylyl cyclase may be enhanced after exposure to a high concentration of β...
- Subjects
BETA adrenoceptors; ADENYLATE cyclase; SMOOTH muscle
- Publication
Clinical & Experimental Pharmacology & Physiology, 2002, Vol 29, Issue 8, p646
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1046/j.1440-1681.2002.03715.x