Molecular mechanism of cibenzoline-induced anticholinergic action in single atrial myocytes: Comparison with effect of disopyramide

S. N. Wu, T. Nakajima, T. Yamashita, E. Hamada, H. Hazama, K. Iwasawa, M. Omata, Y. Kurachi

研究成果: Article同行評審

33 引文 斯高帕斯(Scopus)


The anticholinergic effects of cibenzoline were examined and compared with those of disopyramide in atrial myocytes isolated from guinea pig heart. The tight-seal whole-cell voltage clamp technique was performed with a patch pipette filled with guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3- thiotriphosphate) (GTPγS). In GTP-loaded cells, both acetylcholine (ACh) and adenosine (Ado) induced a specific K channel current through GTP-binding proteins by binding to the muscarinic and Ado receptors, respectively. Both cibenzoline and disopyramide suppressed the ACh-induced K current effectively in a concentration-dependent manner. The concentrations for half-maximal inhibition of the current (EC50) caused by cibenzoline and disopyramide were 8 and 3 μM, respectively. In GTPγS-loaded cells, the K current was irreversibly activated because GTP binding proteins were directly elicited by GTPγS. Cibenzoline effectively caused a decrease in the GTPγS-induced K current, whereas the extent of disopyramide action on the GTPγS-induced K current was much less. Cibenzoline also caused significant inhibition of Ado- induced K current in GTP-loaded cells. However, the action of disopyramide was less effective in inhibiting Ado-induced K current. These results indicate that cibenzoline has less potent anticholinergic effects than disopyramide in atrial myocytes. In addition, cibenzoline effectively inhibits the muscarinic K channel itself and/or GTP-binding proteins coupled to the channel, whereas the effect of disopyramide is attributed mainly to blockade of muscarinic receptors. These findings provide novel understanding of the molecular mechanism of anticholinergic action of cibenzoline.

頁(從 - 到)618-623
期刊Journal of Cardiovascular Pharmacology
出版狀態Published - 1994

All Science Journal Classification (ASJC) codes

  • 藥理
  • 心臟病學與心血管醫學


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