Inhibition of ion channels by hirsutine in rat pheochromocytoma cells.

Abstract

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.

• Authors: K Nakazawa, T Watano, M Ohara-Imaizumi, K Inoue, K Fujimori, Y Ozaki, M Harada, A Takanaka
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 57 Issue 4 Pg. 507-15 (Dec 1991) ISSN: 0021-5198 [Print] Japan
• PMID: 1724991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Calcium Channels
• Ganglionic Blockers
• Hexamethonium Compounds
• Ion Channels
• Potassium Channels
• Receptors, Nicotinic
• Hexamethonium
• Nicotine
• Dopamine
• hirsutine

Topics

• Adrenal Gland Neoplasms (metabolism, pathology)
• Alkaloids (pharmacology)
• Animals
• Calcium Channels (drug effects)
• Dopamine (metabolism)
• Electrophysiology
• Ganglionic Blockers (pharmacology)
• Hexamethonium
• Hexamethonium Compounds (pharmacology)
• Ion Channels (drug effects)
• Nicotine (pharmacology)
• Pheochromocytoma (metabolism, pathology)
• Potassium Channels (drug effects)
• Rats
• Receptors, Nicotinic (drug effects)
• Tumor Cells, Cultured