Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea
| Autor: | Masakazu Yamaguchi, Kenji Nishioka, Masataka Saito, Osamu Shibata, Tetsuji Makita, Koji Sumikawa, Maki Yoshimura |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Contraction (grammar) Monoamine Oxidase Inhibitors Pharmaceutical Science Pharmacology In Vitro Techniques Inhibitory postsynaptic potential Phosphatidylinositols Potassium Chloride chemistry.chemical_compound Selegiline Pi medicine Animals Vasoconstrictor Agents Phosphatidylinositol Rats Wistar Dose-Response Relationship Drug Chemistry Muscle Smooth Smooth muscle contraction Acetylcholine Rats Trachea Monoamine oxidase B medicine.drug Muscle Contraction |
| Zdroj: | The Journal of pharmacy and pharmacology. 56(7) |
| ISSN: | 0022-3573 |
| Popis: | 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 IP1 accumulation were 2.20±0.20 Bq and 7.88±0.23 Bq, respectively, and selegiline at a dose of 1000 μM attenuated ACh-induced IP1 accumulation (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: | OpenAIRE |
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