| Autor: |
Yoshimura, Maki, Shibata, Osamu, Saito, Masataka, Yamaguchi, Masakazu, Nishioka, Kenji, Makita, Tetsuji, Sumikawa, Koji |
| Zdroj: |
Journal of Pharmacy and Pharmacology; July 2004, Vol. 56 Issue: 7 p935-939, 5p |
| Abstrakt: |
Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca2+concentration. Since intracellular Ca2+is partly regulated by phosphatidylinositol (PI) response and is important for smooth muscle contraction, selegiline may affect airway smooth muscle tension. We examined the effects of selegiline on acetylcholine (ACh)‐ and KCl‐induced contractile and PI responses in rat trachea. The trachea was cut into 3‐mm‐wide ring segments or 1‐mm‐wide slices. ACh (3 μM, 50% effective dose) or KCl (40mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [3H]myo‐inositol and 3 μM ACh in the presence of selegiline, and [3H]inositol monophosphate (IP1) was measured. Selegiline dose‐dependently attenuated ACh‐ and KCl‐induced tracheal ring contractions. Fifty‐percent inhibitory doses (ID50) of selegiline against ACh‐ and KCl‐induced contraction were 120±30 μM and 80±20 μM, respectively. Basal and ACh‐induced IP1accumulation were 2.20±0.20 Bq and 7.88±0.23 Bq, respectively, and selegiline at a dose of 1000 μM attenuated ACh‐induced IP1accumulation (5.44±0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage‐operated Ca2+channels and the PI response. |
| Databáze: |
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