Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea.
Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca(2+) concentration. Since intracellular Ca(2+) 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 microM, 50% effective dose) or KCl (40 mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [(3)H]myo-inositol and 3 microM ACh in the presence of selegiline, and [(3)H]inositol monophosphate (IP(1)) 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 microM and 80 +/- 20 microM, respectively. Basal and ACh-induced IP(1) accumulation were 2.20 +/- 0.20 Bq and 7.88 +/- 0.23 Bq, respectively, and selegiline at a dose of 1000 microM attenuated ACh-induced IP(1) accumulation (5.44 +/- 0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage-operated Ca(2+) channels and the PI response.
Yoshimura
Maki
M
Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
Shibata
Osamu
O
Saito
Masataka
M
Yamaguchi
Masakazu
M
Nishioka
Kenji
K
Makita
Tetsuji
T
Sumikawa
Koji
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010716:Phosphatidylinositols; D014662:Vasoconstrictor Agents; D012642:Selegiline; D011189:Potassium Chloride; D000109:Acetylcholine