PMID- 7516012
OWN - NLM
STAT- MEDLINE
DCOM- 19940708
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 23
IP  - 4
DP  - 1994 Apr
TI  - Molecular mechanism of cibenzoline-induced anticholinergic action in single 
      atrial myocytes: comparison with effect of disopyramide.
PG  - 618-23
AB  - 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) (GTP gamma 
      S). 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 microM, respectively. In GTP 
      gamma S-loaded cells, the K current was irreversibly activated because GTP 
      binding proteins were directly elicited by GTP gamma S. Cibenzoline effectively 
      caused a decrease in the GTP gamma S-induced K current, whereas the extent of 
      disopyramide action on the GTP gamma S-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.
FAU - Wu, S N
AU  - Wu SN
AD  - 2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 
      Japan.
FAU - Nakajima, T
AU  - Nakajima T
FAU - Yamashita, T
AU  - Yamashita T
FAU - Hamada, E
AU  - Hamada E
FAU - Hazama, H
AU  - Hazama H
FAU - Iwasawa, K
AU  - Iwasawa K
FAU - Omata, M
AU  - Omata M
FAU - Kurachi, Y
AU  - Kurachi Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Imidazoles)
RN  - 0 (Parasympatholytics)
RN  - 0 (Potassium Channels)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Receptors, Purinergic P1)
RN  - GFO928U8MQ (Disopyramide)
RN  - Z7489237QT (cifenline)
SB  - IM
MH  - Animals
MH  - Disopyramide/*pharmacology
MH  - Guinea Pigs
MH  - Heart Atria/cytology/*drug effects
MH  - Imidazoles/*pharmacology
MH  - In Vitro Techniques
MH  - Parasympatholytics/*pharmacology
MH  - Potassium Channels/drug effects
MH  - Receptors, Muscarinic/drug effects
MH  - Receptors, Purinergic P1/drug effects
EDAT- 1994/04/01 00:00
MHDA- 1994/04/01 00:01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 1994/04/01 00:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
AID - 10.1097/00005344-199404000-00014 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 1994 Apr;23(4):618-23. doi: 
      10.1097/00005344-199404000-00014.