TY - JOUR
T1 - The specific binding of [3H]EO-122, a radiolabeled class I antiarrhythmic drug to rat heart membranes
AU - Oppenheimer, Edna
AU - Meiri, Hamutal
AU - Ori, Yaacov
N1 - Funding Information:
Acknowledgements This work was supported by a grant from the Israel Ministry of Health. We are indebted to Professor Sasson Cohen from this department for his continuous encouragement and inner-est. The excellent technical help of MS Ra.ya Singer is also highly appreciated.
PY - 1989/2
Y1 - 1989/2
N2 - [3H]EO-122, a radiolabeled class I antiarrhythmic drug, has been used to characterize a new specific binding system to rat heart membranes. The binding is saturable and competitive with unlabeled EO-122 and other antiarrhythmic drugs. In this system, [3H]EO-122 binds to two sites. Site A with an apparent Kd of 33.5 ± 1.5 nm, Bmax of 1.05 ± 0.15 pmol/mg protein and Hill coefficient nH = 4. Site B with an apparent Kd of 233 ± 25 nm, Bmax equals 5.7 ± 0.61 pmol/mg proteins and nH = 6. The binding to site B indicates that this site is pharmacologically relevant to known class IA antiarrhythmic drugs such as quinidine and procainamide. Lidocaine (class IB) does not interact with this site. Interpretation of the high Hill coefficient suggests that the binding of an antiarrhythmic drug to its pharmacologically relevant binding site exposes additional binding sites and/or modulates the affinity of adjacent binding sites.
AB - [3H]EO-122, a radiolabeled class I antiarrhythmic drug, has been used to characterize a new specific binding system to rat heart membranes. The binding is saturable and competitive with unlabeled EO-122 and other antiarrhythmic drugs. In this system, [3H]EO-122 binds to two sites. Site A with an apparent Kd of 33.5 ± 1.5 nm, Bmax of 1.05 ± 0.15 pmol/mg protein and Hill coefficient nH = 4. Site B with an apparent Kd of 233 ± 25 nm, Bmax equals 5.7 ± 0.61 pmol/mg proteins and nH = 6. The binding to site B indicates that this site is pharmacologically relevant to known class IA antiarrhythmic drugs such as quinidine and procainamide. Lidocaine (class IB) does not interact with this site. Interpretation of the high Hill coefficient suggests that the binding of an antiarrhythmic drug to its pharmacologically relevant binding site exposes additional binding sites and/or modulates the affinity of adjacent binding sites.
KW - Antiarrhythmic drugs
KW - Antiarrhythmic receptor
KW - Class I
KW - Radioreceptor assay
KW - [H]EO-122
UR - http://www.scopus.com/inward/record.url?scp=0024472679&partnerID=8YFLogxK
U2 - 10.1016/0022-2828(89)90864-X
DO - 10.1016/0022-2828(89)90864-X
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AN - SCOPUS:0024472679
VL - 21
SP - 223
EP - 230
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 2
ER -