Lack of effect of Z-butylidenephthalide on presynaptic N-type Ca2+ channels in isolated Guinea-pig ileum

Marcelo Chen, Wun Chang Ko

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Z-Butylidenephthalide (Bdph) was reported to more potently inhibit electrically induced twitch responses than acetylcholine-induced tonic contraction in isolated Guinea-pig ileum (GPI). The aim of the present study was to investigate the inhibitory effects of Z-Bdph on Ca2+ and K+ channels on GPI. In Locke-Ringer's solution, both responses were isometrically recorded on a polygraph. Incubation of ω-conotoxin MVIIC, but not Z-Bdph, in the electrically stimulated GPI prior to adding ω-conotoxin GVIA, an irreversible blocker of N-type voltage-dependent Ca2+ channels (VDCCs), protected the binding sites and resulted in the twitch responses reversible by washing, suggesting that Z-Bdph did not bind to the N-type VDCCs. Interestingly, we found Z-Bdph concentration dependently delayed the onsets of K+-induced twitch responses, suggesting that Z-Bdph may be a blocker of K+ channels to interfere extracellular K+ across through the pre-junctional membrane of nerve ending in K+-free medium. Z-Bdph similar to nifedipine non-competitively inhibited cumulative ACh-induced phasic contractions, suggesting that Z-Bdph may bind to L-type of inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ channels on the endoplasmic reticulum (ER) membrane. In the presence of verapamil, a L-type Ca2+ channel blocker or Z-Bdph, the twitch inhibitions by either were effectively reversed by exogenous Ca2+, suggesting that they may freely pass through pre-junctional N-type, but not L-type which was blocked at least a part by either, of VDDCs open when each electrical coaxial stimulation (ECS) into intracellular space of cholinergic nerve terminal and trigger release of transmitters. In conclusion, results confirm that Z-Bdph more potently inhibits ECS-induced twitch responses than ACh-induced PCs in GPI and suggest that this effect is not mediated by interaction with presynaptic N-type VDCCs.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume389
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Keywords

  • Acetylcholine
  • Electrically induced twitch response
  • Guinea-pig ileum
  • Nifedipine
  • Z-Butylidenephthalide
  • ω-Conotoxin GVIA

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Lack of effect of Z-butylidenephthalide on presynaptic N-type Ca<sup>2+</sup> channels in isolated Guinea-pig ileum'. Together they form a unique fingerprint.

Cite this