Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017

De Zai Dai, Hui Juan Hu, Jing Zhao, Xue Mei Hao, Dong Mei Yang, Pei Ai Zhou, Cai Hong Wu

Research output: Contribution to journalArticle

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Abstract

AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca2+-related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC50 was 11.5 μmol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 μmol/L in KH solution (phase 1), Ca2+ free KH solution (phase 2), and by addition of CaCl2 into Ca2+-free KH solution (phase 3) were observed. The IC50 to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-dependent channel (VDC) was 0.324 μmol/L and 16.3 μmol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca2+ entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively. CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.

Original languageEnglish (US)
Pages (from-to)416-423
Number of pages8
JournalActa Pharmacologica Sinica
Volume25
Issue number4
StatePublished - Apr 1 2004
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Keywords

  • 4-Chlorobenzyltetrahydroberine
  • Berberine
  • Calcium
  • Myocardium
  • Patch-clamp techniques
  • Vascular smooth muscle

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