Inhibition of ion channels by hirsutine in rat pheochromocytoma cells.
Effects of hirsutine, an alkaloid that produces a potent ganglion blocking effect, were investigated using rat pheochromocytoma PC12 cells. Hirsutine (1 to 10 microM) suppressed dopamine-release evoked by 100 microM nicotine. In voltage-clamped cells, hirsutine (1 to 10 microM) inhibited the inward current activated by 100 microM nicotine. Hirsutine was equipotent to hexamethonium in blocking the nicotine-activated current. The voltage-dependency of the nicotine activated current was not modified by hirsutine. Effects of hirustine on other ion channels were tested to determine its selectivity. Inward currents mediated through ATP-activated channels were scarcely affected by hirsutine (up to 100 microM). However, hirustine (10 microM) inhibited Ba currents passing through Ca channels and K currents activated by depolarizing voltage steps. The results suggest that hirsutine potently blocks nicotinic receptor-channels, but hirsutine also inhibits voltage-gated Ca and K channels. Roles of the inhibition of these channels in the pharmacological effects of hirsutine were discussed.
Nakazawa
K
K
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Watano
T
T
Ohara-Imaizumi
M
M
Inoue
K
K
Fujimori
K
K
Ozaki
Y
Y
Harada
M
M
Takanaka
A
A
D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D015220:Calcium Channels; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D007473:Ion Channels; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D009538:Nicotine; D004298:Dopamine; C038369:hirsutine