The Mechanism of Inhibitory Actions of S-Petasin, a Sesquiterpene ofPetasites formosanus, on L-Type Calcium Current in NG108-15 Neuronal Cells

Abstract

The effects of S-petasin, a sesquiterpene isolated from Petasites formosanus Kitamura, on ion currents in a mouse neuroblastoma and a rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. S-Petasin (1 - 300 microM) caused a decrease in the amplitude of L-type Ca2+ current (I(Ca,L)) in a concentration-dependent manner, however, it did not change the overall shape of the current-voltage relationship of I(Ca,L). The IC50 value for S-petasin-induced inhibition of I(Ca,L) was 11 microM. S-Petasin (10 microM) shifted the steady-state inactivation of I(Ca,L) to a more negative membrane potential by approximately -10 mV. S-petasin could prolong the recovery of I(Ca,L) inactivation. The inhibitory effect of S-petasin on I(Ca,L) was found to exhibit tonic and use-dependent characteristics. S-Petasin could inhibit I(Ca,L) evoked by action potential waveforms effectively. S-Petasin also suppressed low voltage-activated I(Ca,L) in NG108-15 cells. S-Petasin at a concentration of 100 microM had little effect on voltage-dependent Na+ current; however, it did produce an inhibitory effect on delayed rectifier K+ current in a time-dependent manner. These results demonstrate that S-petasin can interact directly with L-type Ca2+ channels in NG108-15 cells. These effects could contribute to the regulation of neuronal activity if similar results were found in neurons in vivo.

Petasites hybridusExtractsin vitroInhibit COX-2 and PGE2Release by Direct Interaction with the Enzyme and by Preventing p42/44 MAP Kinase Activation in Rat Primary Microglial Cells

“…The negative chronotropic and inotropic properties of S-petasin also can be attributed mainly to inhibition of voltage-dependent Ca 2+ channels but not to blockade of dihydropyridine binding sites of L-type Ca 2+ channel or to muscarinic receptor activation [29]. Direct affection of L-type Ca 2+ channels by S-petasin was also found in NG108 ± 15 neuronal cells [30]. S-Isopetasin allosterically antagonizes carbachol in isolated guinea pig atria [31].…”

S‐Petasin, the Main Sesquiterpene of Petasites formosanus, Inhibits Phosphodiesterase Activity and Suppresses Ovalbumin‐Induced Airway Hyperresponsiveness

“…In the present in vitro results, S -petasin (30–100  μ M), but not at 300  μ M which is beyond a physiological condition, did not inhibit cumulative OVA-induced contractions of isolated sensitized guinea pig trachealis, which were unaffected by 1  μ M nifedipine, suggesting that S -petasin does not inhibit degranulation or activation of mast cells [57]. Indeed, S -petasin was reported to be an L-type voltage-dependent Ca 2+ channel blocker in rat aortic smooth muscle cells [58, 59] and in mouse NG 108-15 neuronal cells [60]. In these neuronal cells, a higher concentration (100  μ M) of S -petasin was also reported to inhibit the delayed rectifier K + current in a time-dependent manner, suggesting that such a blockage does not seem to be instantaneous, but develops with time after the channels are opened [60].…”

“…Indeed, S -petasin was reported to be an L-type voltage-dependent Ca 2+ channel blocker in rat aortic smooth muscle cells [58, 59] and in mouse NG 108-15 neuronal cells [60]. In these neuronal cells, a higher concentration (100  μ M) of S -petasin was also reported to inhibit the delayed rectifier K + current in a time-dependent manner, suggesting that such a blockage does not seem to be instantaneous, but develops with time after the channels are opened [60]. The blockage by S -petasin may contribute to the regulation of neuronal activity, but not to relaxation of the trachea-bronchial tree.…”

A botanical and pharmacological description of petasites species

“…They both inhibit the synthesis of peptide-leukotriene, whilst petasin also blocks the release of the eosinophil cationic protein [35]. Additionally, petasin inhibits contractions induced by histamine, carbachol, and the accumulation of calcium ions [19,41,44]. It follows that non-specific antispasmodic and antimuscarinic effects are responsible for the myorelaxant activity of petasin [2].…”