TY - JOUR
T1 - Differential antagonism of the negative inotropic effect of gentamicin by calcium ions, Bay K 8644 and isoprenaline in canine ventricular muscle
T2 - Comparison with cobalt ions
AU - Hashimoto, H.
AU - Yanagisawa, T.
AU - Taira, N.
PY - 1989
Y1 - 1989
N2 - 1. Gentamicin (10-4-10-2 M) and Co2+ (10-4-10-2 M) produced a decrease in developed tension of canine isolated ventricular muscles leading to near abolition at 10-2 M. Their negative inotropic effects developed rapidly and wore off shortly after wash-out. 2. The concentration-negative inotropic effect curves for gentamicin were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of Bay K 8644 (10-7-10-5 M) or isoprenaline (10-7-10-5 M). IC50 values for gentamicin increased about 3-fold with about a 6 fold increase in external Ca2+. The Schild plot yielded a pA2 of 2.29 for Ca2+ and its slope was -1.17 (r = -0.79). 3. The concentration-negative inotropic effect curves for Co2+ were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of isoprenaline (10-7-10-5 M). IC50 values for Co2+ increased about 5-fold with about a 6-fold increase in external Ca2+. The Schild plot gave a pA2 value of 2.60 for Ca2+ and its slope was -1.11 (r = -0.86). 4. The concentration-positive inotropic effect curves for Ca2+, which were computer-fitted to a logistic equation, gave 2.88 x 10-3 M for EC50. This value was very close to the K(Ca) calculated from pA2 values for Ca2+ based on antagonism between gentamicin or Co2+ and Ca2+ (5.13 x 10-3 and 2.51 x 10-3 M). 5. It is concluded that like Co2+, gentamicin molecules compete with Ca2+ for the same binding sites presumably located at the outer orifice of Ca-channels in the cardiac sarcolemma.
AB - 1. Gentamicin (10-4-10-2 M) and Co2+ (10-4-10-2 M) produced a decrease in developed tension of canine isolated ventricular muscles leading to near abolition at 10-2 M. Their negative inotropic effects developed rapidly and wore off shortly after wash-out. 2. The concentration-negative inotropic effect curves for gentamicin were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of Bay K 8644 (10-7-10-5 M) or isoprenaline (10-7-10-5 M). IC50 values for gentamicin increased about 3-fold with about a 6 fold increase in external Ca2+. The Schild plot yielded a pA2 of 2.29 for Ca2+ and its slope was -1.17 (r = -0.79). 3. The concentration-negative inotropic effect curves for Co2+ were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of isoprenaline (10-7-10-5 M). IC50 values for Co2+ increased about 5-fold with about a 6-fold increase in external Ca2+. The Schild plot gave a pA2 value of 2.60 for Ca2+ and its slope was -1.11 (r = -0.86). 4. The concentration-positive inotropic effect curves for Ca2+, which were computer-fitted to a logistic equation, gave 2.88 x 10-3 M for EC50. This value was very close to the K(Ca) calculated from pA2 values for Ca2+ based on antagonism between gentamicin or Co2+ and Ca2+ (5.13 x 10-3 and 2.51 x 10-3 M). 5. It is concluded that like Co2+, gentamicin molecules compete with Ca2+ for the same binding sites presumably located at the outer orifice of Ca-channels in the cardiac sarcolemma.
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U2 - 10.1111/j.1476-5381.1989.tb11901.x
DO - 10.1111/j.1476-5381.1989.tb11901.x
M3 - Article
C2 - 2472847
AN - SCOPUS:0024554407
VL - 96
SP - 906
EP - 912
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 4
ER -